MHC class II antigen presentation (Homo sapiens)

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6, 12, 34, 58, 6410, 5318, 24, 28, 42, 43, 57...29, 5528, 34, 36, 4216, 25, 37, 39, 50...10, 684, 6821, 29, 31293, 4, 9, 15, 40...26, 523, 4, 9, 15, 40...1, 14, 22, 60, 635, 29, 46, 5544, 5617, 35, 512, 17, 20, 27, 35...7, 8, 19, 3221, 29, 30, 684611, 13, 33, 47, 7010, 45, 6835, 38, 41, 5123, 48, 49, 59, 60, 62...alpha beta dimerIi trimercalnexin trans-Golgi network membraneKinesins MHC class II alpha/beta dimer Invariant chain trimer Dynactin RILP dimer KIF2B dimer Sar1bGTPSec23pSec24pSec13pSec31p Complex peptide loaded MHC class II Golgi membraneHLA II beta chain KinesinsDynactinmicrotubule HLA-DM/HLA-DO KIF4B homodimer HLA II beta chain integral to lumenal side of endoplasmic reticulum membraneNonameric complex KIF15 dimer Sar1bGTP Complex HLA II alpha chain Clathrin Triskelion Sec13pSec31p Complex HLA II alpha chain Invariant chain trimer KIF3A partners Nonameric complex HLA II alpha chain MHC class II alpha/beta/Ii nonamer MCAK dimer MHC II alpha beta heterodimer AP-1 mu Invariant chain trimer Adaptor protein 2 complex Clathrin Invariant chain trimer HLA II beta chain Adaptor protein complex 2 HLA II beta chain Invariant chain trimer HLA II beta chain HLA II beta chain Nonameric complex Clathrin AP-2 complex HLA II beta chain HLA II beta chain lip10 trimer MHC II alpha/beta dimer CENP-E dimer Arf1-GDP MHC II alpha/beta dimer HLA II alpha chain AP-1 Complex MHC class II alpha/beta dimer Nonameric complex lip22 trimer HLA II alpha chain Clathrin-coated vesicle MHC IIlip22 nonamer HLA II alpha chain HLA-DO AP-1 sigma TGN-lysosome vesicle with nonameric complex DHC dimer Nonameric complex Invariant chain trimer HLA II alpha chain HLA II alpha chain clathrin-coated endocytic vesicleClathrin-coated vesicle AP-1 sigma HLA II alpha chain Invariant chain trimer MHC II alpha/beta dimer Nonameric complex in COPII vesicle Kinesin-2 DLIs MHC II alpha/beta dimer Clathrin coated MHC class II alpha/beta/Ii nonamer Invariant chain trimer HLA II alpha chain peptide loaded MHC class II HLA-DMHLA-DO MHC II alpha/beta dimer AP-1 sigma Sec24 KIF4A homodimer KIF18A dimer MHC II alpha beta heterodimer Clathrin Kinesin-1 HLA II alpha chain HLA II alpha chain Sar1bGTPSec23pSec24p AP-2 complex Adaptor protein complex 2 Kinesin-5 homotetramer HLA II beta chain Sec23pSec24p Complex Clathrin-coated vesicle Dynactin ER to Golgi transport vesicleHLA II beta chain HLA II beta chain HLA II beta chain Invariant chain trimer AP-1 Clathrin coated nonameric complex HLA II alpha chain HLA II alpha chain DLCs HLA-DM HLA II alpha chain MHC class II alpha/beta/Ii nonamer HLA II beta chain Adaptor protein complex 2 AP-1 mu HLA II alpha chain Kinesin-13 dimers HLA II beta chain HLA II beta chain Nonameric complex Invariant chain trimer Centralspindlin HLA II alpha chain Clathrin Invariant chain trimer Sec13pSec31p Complex KIF2A dimer MHC II alpha/beta dimer endoplasmic reticulum membraneMHC II alpha/beta dimer Clathrin-coated vesicle MHC class II alpha/beta dimer MHC class II alpha/beta/Ii nonamer Nonameric complex cytosollysosomal lumenKinesin-4 homodimers MHC II alpha/beta dimer MHC II alpha beta heterodimer HLA II alpha chain HLA II beta chain Clathrin RAB7AGTP Sec24 transport vesicleAP-1 mu Dynein complex HLA II alpha chain peptide free MHC IIHLA-DM MHC II alpha beta heterodimer Sec23pSec24p Complex DyneinDynactinmicrotubule MHC class II alpha/beta dimer HLA II beta chain AP-1 Complex HLA II beta chain Kinesin-10 Sar1bGTP Complex MHC class II alpha/beta/Ii nonamer Clathrin coated MHC class II alpha/beta/Ii nonamer HLA II beta chain MHC class II alpha/beta dimer MHC IICLIP Invariant chain trimer HLA II beta chain Sar1bGTPSec23pSec24pSec13pSec31p Complex MHC II alpha/beta dimer Chromokinesin dimers Adaptor protein 2 complex MHC II alpha/beta dimer HLA II beta chain Clathrin AP-1 Complex Adaptor protein complex 2 Invariant chain trimer HLA II alpha chain Invariant chain trimer MHC II alpha/beta dimer Arf1-GTP Sar1bGTPSec23pSec24p DICs RAB7RILPORP1L complex HLA II alpha chain DHCs endocytic vesicleNonameric complex MHC IIlip10 nonamer GDPHLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-13 beta chain AP2S1 HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-10 beta chain SEC31A AP-1 Clathrin coated nonameric complexHLA class II histocompatibility antigen, DRB1-9 beta chain precursor DYNC1I2 HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DQ SEC23A HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor CLTC-1 HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DO alpha chain precursor HLA class II histocompatibility antigen, DRB1-4 beta chain KIF4A HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-16 beta chain DCTN1 HLA class II histocompatibility antigen, DRB1-16 beta chain CD74 HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ CathepsinDCTN3HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DR beta 4 chain GTP HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DP alpha chain precursor unfolded antigenSPTBN2HLA class II histocompatibility antigen, DRB1-14 beta chain RAB7A HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DRB1-14 beta chain KIF2B HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DR beta 4 chain CD74 HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-7 beta chain AP1M1 HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-10 beta chain Clathrin light chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor AP2B1 CD74 HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DQ beta 2 chain SH3GL2 HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DQ CLTC1-1 HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DR alpha chain precursor Clathrin TriskelionHLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DQ beta 2 chain AntigenHLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-4 beta chain MHC class II epitopesHLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-8 beta chain CD74 SEC24A HLA class II histocompatibility antigen, DP alpha chain precursor DCTN5 HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DQ beta 2 chain KIF3B CLTA CD74Clathrin light chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-11 beta chain MHC IIlip22 nonamerHLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-9 beta chain precursor AP1B1 HLA class II histocompatibility antigen, DRB1-1 beta chain MHC IIlip10 nonamerSEC23A HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR alpha chain precursor AP2B1 HLA class II histocompatibility antigen, DR beta 5 chain SEC24B HLA class II histocompatibility antigen, DRB1-13 beta chain KIF22 AP2A2DYNC2H1 HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-1 beta chain AP-1 ComplexHLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DR beta 5 chain Clathrin-coated vesicleHLA class II histocompatibility antigen, DR alpha chain precursor GDPCD74 HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor DCTN6 HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-11 beta chain CANXHLA class II histocompatibility antigen, DRB1-10 beta chain Clathrin coated MHC class II alpha/beta/Ii nonamerHLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DR beta 5 chain peptide loaded MHC class IIHLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor Nonameric complexCD74AP1S3 HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain AP2M1 DCTN3Clathrin light chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-11 beta chain AP1S2 SH3GL2HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB1-4 beta chain AP2B1 HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DR beta 4 chain AP1S3 AP1B1 CENPE HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DQ CD74 HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DP CLTA HLA class II histocompatibility antigen, DRB1-11 beta chain GTP AP2M1 CLTC-1 HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain CANX HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DQ GTP CD74 Arf1-GTPCD74 AP2M1 HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain RACGAP1 Clathrin light chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-11 beta chain SEC24D HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DQ ARF1AP2A1 HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-1 beta chain AP2B1 HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DP AP2A1 Clathrin-coated vesicleHLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA-DM/HLA-DOHLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DQ AP2A1 HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DQ SAR1B HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-4 beta chain AP2A2SEC13 KIF18A DYNLL2 HLA class II histocompatibility antigen, DRB1-4 beta chain peptide loaded MHC class IIARF1HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-10 beta chain DYNC1LI2 HLA class II histocompatibility antigen, DRB1-14 beta chain CLTC1-1 CD74CathepsinHLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DQ AP2M1 HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DQ AP2S1 KIF15 HLA class II histocompatibility antigen, DP H2ODCTN4CD74 HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB1-13 beta chain Nonameric complexHLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain KIF11 HLA class II histocompatibility antigen, DRB3-1 beta chain precursor KIF4B HLA class II histocompatibility antigen, DO beta chain precursor HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain DCTN5 HLA class II histocompatibility antigen, DM alpha chain precursor HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor Nonameric complexHLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain KinesinsDynactinmicrotubuleGDP HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DR beta 4 chain RILP LGMNHLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain AP1S2 HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain MHC II alpha beta heterodimerHLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain KIF2C HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DQ SEC24A HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DRB1-11 beta chain CD74 HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-12 beta chain MHC class II alpha/beta/Ii nonamerClathrin coated MHC class II alpha/beta/Ii nonamerHLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DR alpha chain precursor DYNC1H1 HLA class II histocompatibility antigen, DRB1-15 beta chain AP1M2HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-8 beta chain CLTC-1 Invariant chain trimerHLA class II histocompatibility antigen, DRB3-1 beta chain precursor CD74 HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DQ KIF3A SEC24C HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain DYNLL1 SAR1B DCTN2 HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DP SEC13 HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA II beta chainHLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain SEC31A HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor CD74HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain AP1M2HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-1 beta chain PiHLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor PiKIF3C HLA class II histocompatibility antigen, DR alpha chain precursor AP1G1 MHC II alpha beta heterodimerHLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-12 beta chain Nonameric complexARP-1HLA class II histocompatibility antigen, DQ TGN-lysosome vesicle with nonameric complexHLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-11 beta chain DCTN6 HLA class II histocompatibility antigen, DR-1 beta chain precursor AP2A2HLA class II histocompatibility antigen, DRB1-11 beta chain AP1M1 HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-16 beta chain KIFAP3 HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-15 beta chain DYNC1I1 HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain GTPHLA class II histocompatibility antigen, DRB1-14 beta chain RAB7RILPORP1L complexHLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-8 beta chain AP2A2HLA class II histocompatibility antigen, DQ ADPpeptide free MHC IIHLA-DMHLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor DCTN4Clathrin light chain KIF2A HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DR alpha chain precursor KIF26A HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DP SEC24C HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DR alpha chain precursor SH3GL2DCTN1 Nonameric complex in COPII vesicleHLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DP alpha chain precursor ATPSar1bGTPSec23pSec24pSec13pSec31p ComplexHLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DP CD74 HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-13 beta chain AP1G1 HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR-1 beta chain precursor AP1S1 Arf1-GDPHLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DM beta chain precursor HLA class II histocompatibility antigen, DQ OSBPL1A AP1M1 HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain CathepsinHLA class II histocompatibility antigen, DRB1-10 beta chain AP1S3 AP1B1 AP2S1 HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor DCTN2 HLA class II histocompatibility antigen, DRB3-1 beta chain precursor DynaminHLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DR beta 4 chain AntigenHLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-10 beta chain alpha beta dimerIi trimercalnexinHLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-16 beta chain CD74 AP2A1 HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DQ AP1G1 HLA class II histocompatibility antigen, DQ beta 2 chain MHC IICLIPAP1S1 DyneinDynactinmicrotubuleHLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DRB1-4 beta chain AP1S2 HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DP HLA II alpha chainSEC24D HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DP alpha chain precursor AP2S1 Dynamin-1/2/3HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR-1 beta chain precursor AP1S1 HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-16 beta chain GTPHLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain SEC24B HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain MHC class II alpha/beta/Ii nonamerHLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-4 beta chain GTP Nonameric complexHLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DP IFI30CD74 HLA class II histocompatibility antigen, DRB1-12 beta chain DYNC2LI1 AP1M2PiHLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-15 beta chain


Description

Antigen presenting cells (APCs) such as B cells, dendritic cells (DCs) and monocytes/macrophages express major histocompatibility complex class II molecules (MHC II) at their surface and present exogenous antigenic peptides to CD4+ T helper cells. CD4+ T cells play a central role in immune protection. On their activation they stimulate differentiation of B cells into antibody-producing B-cell blasts and initiate adaptive immune responses. MHC class II molecules are transmembrane glycoprotein heterodimers of alpha and beta subunits. Newly synthesized MHC II molecules present in the endoplasmic reticulum bind to a chaperone protein called invariant (Ii) chain. The binding of Ii prevents the premature binding of self antigens to the nascent MHC molecules in the ER and also guides MHC molecules to endocytic compartments. In the acidic endosomal environment, Ii is degraded in a stepwise manner, ultimately to free the class II peptide-binding groove for loading of antigenic peptides. Exogenous antigens are internalized by the APC by receptor mediated endocytosis, phagocytosis or pinocytosis into endocytic compartments of MHC class II positive cells, where engulfed antigens are degraded in a low pH environment by multiple acidic proteases, generating MHC class II epitopes. Antigenic peptides are then loaded into the class II ligand-binding groove. The resulting class II peptide complexes then move to the cell surface, where they are scanned by CD4+ T cells for specific recognition (Berger & Roche 2009, Zhou & Blum 2004, Watts 2004, Landsverk et al. 2009). Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=2132295

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Bibliography

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  1. Rocha N, Kuijl C, van der Kant R, Janssen L, Houben D, Janssen H, Zwart W, Neefjes J.; ''Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning.''; PubMed Europe PMC Scholia
  2. Landsverk OJ, Barois N, Gregers TF, Bakke O.; ''Invariant chain increases the half-life of MHC II by delaying endosomal maturation.''; PubMed Europe PMC Scholia
  3. Hemon P, Jean-Louis F, Ramgolam K, Brignone C, Viguier M, Bachelez H, Triebel F, Charron D, Aoudjit F, Al-Daccak R, Michel L.; ''MHC class II engagement by its ligand LAG-3 (CD223) contributes to melanoma resistance to apoptosis.''; PubMed Europe PMC Scholia
  4. Sandoval IV, Bakke O.; ''Targeting of membrane proteins to endosomes and lysosomes.''; PubMed Europe PMC Scholia
  5. Villadangos JA, Bryant RA, Deussing J, Driessen C, Lennon-Duménil AM, Riese RJ, Roth W, Saftig P, Shi GP, Chapman HA, Peters C, Ploegh HL.; ''Proteases involved in MHC class II antigen presentation.''; PubMed Europe PMC Scholia
  6. Urban RG, Chicz RM, Strominger JL.; ''Selective release of some invariant chain-derived peptides from HLA-DR1 molecules at endosomal pH.''; PubMed Europe PMC Scholia
  7. Raddrizzani L, Bono E, Vogt AB, Kropshofer H, Gallazzi F, Sturniolo T, Hämmerling GJ, Sinigaglia F, Hammer J.; ''Identification of destabilizing residues in HLA class II-selected bacteriophage display libraries edited by HLA-DM.''; PubMed Europe PMC Scholia
  8. Bania J, Gatti E, Lelouard H, David A, Cappello F, Weber E, Camosseto V, Pierre P.; ''Human cathepsin S, but not cathepsin L, degrades efficiently MHC class II-associated invariant chain in nonprofessional APCs.''; PubMed Europe PMC Scholia
  9. Villadangos JA.; ''Presentation of antigens by MHC class II molecules: getting the most out of them.''; PubMed Europe PMC Scholia
  10. Dixon AM, Stanley BJ, Matthews EE, Dawson JP, Engelman DM.; ''Invariant chain transmembrane domain trimerization: a step in MHC class II assembly.''; PubMed Europe PMC Scholia
  11. Hastings KT, Lackman RL, Cresswell P.; ''Functional requirements for the lysosomal thiol reductase GILT in MHC class II-restricted antigen processing.''; PubMed Europe PMC Scholia
  12. Kageyama T, Yonezawa S, Ichinose M, Miki K, Moriyama A.; ''Potential sites for processing of the human invariant chain by cathepsins D and E.''; PubMed Europe PMC Scholia
  13. Anderson KS, Cresswell P.; ''A role for calnexin (IP90) in the assembly of class II MHC molecules.''; PubMed Europe PMC Scholia
  14. Salamero J, Le Borgne R, Saudrais C, Goud B, Hoflack B.; ''Expression of major histocompatibility complex class II molecules in HeLa cells promotes the recruitment of AP-1 Golgi-specific assembly proteins on Golgi membranes.''; PubMed Europe PMC Scholia
  15. Hofmann MW, Höning S, Rodionov D, Dobberstein B, von Figura K, Bakke O.; ''The leucine-based sorting motifs in the cytoplasmic domain of the invariant chain are recognized by the clathrin adaptors AP1 and AP2 and their medium chains.''; PubMed Europe PMC Scholia
  16. Kropshofer H, Vogt AB, Moldenhauer G, Hammer J, Blum JS, Hämmerling GJ.; ''Editing of the HLA-DR-peptide repertoire by HLA-DM.''; PubMed Europe PMC Scholia
  17. Deussing J, Roth W, Saftig P, Peters C, Ploegh HL, Villadangos JA.; ''Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation.''; PubMed Europe PMC Scholia
  18. Bard F, Malhotra V.; ''The formation of TGN-to-plasma-membrane transport carriers.''; PubMed Europe PMC Scholia
  19. Marić MA, Taylor MD, Blum JS.; ''Endosomal aspartic proteinases are required for invariant-chain processing.''; PubMed Europe PMC Scholia
  20. Nakagawa T, Roth W, Wong P, Nelson A, Farr A, Deussing J, Villadangos JA, Ploegh H, Peters C, Rudensky AY.; ''Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus.''; PubMed Europe PMC Scholia
  21. Watts C, Matthews SP, Mazzeo D, Manoury B, Moss CX.; ''Asparaginyl endopeptidase: case history of a class II MHC compartment protease.''; PubMed Europe PMC Scholia
  22. Doherty GJ, McMahon HT.; ''Mechanisms of endocytosis.''; PubMed Europe PMC Scholia
  23. Wolf PR, Ploegh HL.; ''How MHC class II molecules acquire peptide cargo: biosynthesis and trafficking through the endocytic pathway.''; PubMed Europe PMC Scholia
  24. Zhang T, Maekawa Y, Hanba J, Dainichi T, Nashed BF, Hisaeda H, Sakai T, Asao T, Himeno K, Good RA, Katunuma N.; ''Lysosomal cathepsin B plays an important role in antigen processing, while cathepsin D is involved in degradation of the invariant chain inovalbumin-immunized mice.''; PubMed Europe PMC Scholia
  25. Dugast M, Toussaint H, Dousset C, Benaroch P.; ''AP2 clathrin adaptor complex, but not AP1, controls the access of the major histocompatibility complex (MHC) class II to endosomes.''; PubMed Europe PMC Scholia
  26. Bakke O, Dobberstein B.; ''MHC class II-associated invariant chain contains a sorting signal for endosomal compartments.''; PubMed Europe PMC Scholia
  27. Gu F, Crump CM, Thomas G.; ''Trans-Golgi network sorting.''; PubMed Europe PMC Scholia
  28. Kropshofer H, Vogt AB, Stern LJ, Hämmerling GJ.; ''Self-release of CLIP in peptide loading of HLA-DR molecules.''; PubMed Europe PMC Scholia
  29. Plüger EB, Boes M, Alfonso C, Schröter CJ, Kalbacher H, Ploegh HL, Driessen C.; ''Specific role for cathepsin S in the generation of antigenic peptides in vivo.''; PubMed Europe PMC Scholia
  30. Kropshofer H, Vogt AB, Thery C, Armandola EA, Li BC, Moldenhauer G, Amigorena S, Hämmerling GJ.; ''A role for HLA-DO as a co-chaperone of HLA-DM in peptide loading of MHC class II molecules.''; PubMed Europe PMC Scholia
  31. Davidson HW.; ''Direct transport of newly synthesized HLA-DR from the trans-Golgi network to major histocompatibility complex class II containing compartments (MIICS) demonstrated using a novel tyrosine-sulfated chimera.''; PubMed Europe PMC Scholia
  32. Shi GP, Bryant RA, Riese R, Verhelst S, Driessen C, Li Z, Bromme D, Ploegh HL, Chapman HA.; ''Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages.''; PubMed Europe PMC Scholia
  33. Motta A, Bremnes B, Morelli MA, Frank RW, Saviano G, Bakke O.; ''Structure-activity relationship of the leucine-based sorting motifs in the cytosolic tail of the major histocompatibility complex-associated invariant chain.''; PubMed Europe PMC Scholia
  34. Shi GP, Villadangos JA, Dranoff G, Small C, Gu L, Haley KJ, Riese R, Ploegh HL, Chapman HA.; ''Cathepsin S required for normal MHC class II peptide loading and germinal center development.''; PubMed Europe PMC Scholia
  35. Roche PA, Marks MS, Cresswell P.; ''Formation of a nine-subunit complex by HLA class II glycoproteins and the invariant chain.''; PubMed Europe PMC Scholia
  36. Freisewinkel IM, Schenck K, Koch N.; ''The segment of invariant chain that is critical for association with major histocompatibility complex class II molecules contains the sequence of a peptide eluted from class II polypeptides.''; PubMed Europe PMC Scholia
  37. McCormick PJ, Martina JA, Bonifacino JS.; ''Involvement of clathrin and AP-2 in the trafficking of MHC class II molecules to antigen-processing compartments.''; PubMed Europe PMC Scholia
  38. Landsverk OJ, Bakke O, Gregers TF.; ''MHC II and the endocytic pathway: regulation by invariant chain.''; PubMed Europe PMC Scholia
  39. Stumptner-Cuvelette P, Benaroch P.; ''Multiple roles of the invariant chain in MHC class II function.''; PubMed Europe PMC Scholia
  40. Wubbolts R, Fernandez-Borja M, Jordens I, Reits E, Dusseljee S, Echeverri C, Vallee RB, Neefjes J.; ''Opposing motor activities of dynein and kinesin determine retention and transport of MHC class II-containing compartments.''; PubMed Europe PMC Scholia
  41. Arunachalam B, Phan UT, Geuze HJ, Cresswell P.; ''Enzymatic reduction of disulfide bonds in lysosomes: characterization of a gamma-interferon-inducible lysosomal thiol reductase (GILT).''; PubMed Europe PMC Scholia
  42. Ramachandra L, Simmons D, Harding CV.; ''MHC molecules and microbial antigen processing in phagosomes.''; PubMed Europe PMC Scholia
  43. Roche PA, Teletski CL, Stang E, Bakke O, Long EO.; ''Cell surface HLA-DR-invariant chain complexes are targeted to endosomes by rapid internalization.''; PubMed Europe PMC Scholia
  44. Ramachandra L, Noss E, Boom WH, Harding CV.; ''Processing of Mycobacterium tuberculosis antigen 85B involves intraphagosomal formation of peptide-major histocompatibility complex II complexes and is inhibited by live bacilli that decrease phagosome maturation.''; PubMed Europe PMC Scholia
  45. Costantino CM, Hang HC, Kent SC, Hafler DA, Ploegh HL.; ''Lysosomal cysteine and aspartic proteases are heterogeneously expressed and act redundantly to initiate human invariant chain degradation.''; PubMed Europe PMC Scholia
  46. Stumptner P, Benaroch P.; ''Interaction of MHC class II molecules with the invariant chain: role of the invariant chain (81-90) region.''; PubMed Europe PMC Scholia
  47. Kropshofer H, Hämmerling GJ, Vogt AB.; ''The impact of the non-classical MHC proteins HLA-DM and HLA-DO on loading of MHC class II molecules.''; PubMed Europe PMC Scholia
  48. Wiendl H, Lautwein A, Mitsdörffer M, Krause S, Erfurth S, Wienhold W, Morgalla M, Weber E, Overkleeft HS, Lochmüller H, Melms A, Tolosa E, Driessen C.; ''Antigen processing and presentation in human muscle: cathepsin S is critical for MHC class II expression and upregulated in inflammatory myopathies.''; PubMed Europe PMC Scholia
  49. Pond L, Kuhn LA, Teyton L, Schutze MP, Tainer JA, Jackson MR, Peterson PA.; ''A role for acidic residues in di-leucine motif-based targeting to the endocytic pathway.''; PubMed Europe PMC Scholia
  50. Roche PA, Cresswell P.; ''Invariant chain association with HLA-DR molecules inhibits immunogenic peptide binding.''; PubMed Europe PMC Scholia
  51. Ramachandra L, Song R, Harding CV.; ''Phagosomes are fully competent antigen-processing organelles that mediate the formation of peptide:class II MHC complexes.''; PubMed Europe PMC Scholia
  52. Neumann J, Koch N.; ''Assembly of major histocompatibility complex class II subunits with invariant chain.''; PubMed Europe PMC Scholia
  53. Johansson M, Rocha N, Zwart W, Jordens I, Janssen L, Kuijl C, Olkkonen VM, Neefjes J.; ''Activation of endosomal dynein motors by stepwise assembly of Rab7-RILP-p150Glued, ORP1L, and the receptor betalll spectrin.''; PubMed Europe PMC Scholia
  54. Wang K, Peterson PA, Karlsson L.; ''Decreased endosomal delivery of major histocompatibility complex class II-invariant chain complexes in dynamin-deficient cells.''; PubMed Europe PMC Scholia
  55. Mellman I.; ''Endocytosis and molecular sorting.''; PubMed Europe PMC Scholia
  56. Ong GL, Goldenberg DM, Hansen HJ, Mattes MJ.; ''Cell surface expression and metabolism of major histocompatibility complex class II invariant chain (CD74) by diverse cell lines.''; PubMed Europe PMC Scholia
  57. Wubbolts R, Fernandez-Borja M, Oomen L, Verwoerd D, Janssen H, Calafat J, Tulp A, Dusseljee S, Neefjes J.; ''Direct vesicular transport of MHC class II molecules from lysosomal structures to the cell surface.''; PubMed Europe PMC Scholia
  58. Bryant PW, Lennon-Duménil AM, Fiebiger E, Lagaudrière-Gesbert C, Ploegh HL.; ''Proteolysis and antigen presentation by MHC class II molecules.''; PubMed Europe PMC Scholia
  59. Kropshofer H, Vogt AB, Hämmerling GJ.; ''Structural features of the invariant chain fragment CLIP controlling rapid release from HLA-DR molecules and inhibition of peptide binding.''; PubMed Europe PMC Scholia
  60. Denzin LK, Sant'Angelo DB, Hammond C, Surman MJ, Cresswell P.; ''Negative regulation by HLA-DO of MHC class II-restricted antigen processing.''; PubMed Europe PMC Scholia
  61. Chow A, Toomre D, Garrett W, Mellman I.; ''Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane.''; PubMed Europe PMC Scholia
  62. Weber DA, Evavold BD, Jensen PE.; ''Enhanced dissociation of HLA-DR-bound peptides in the presence of HLA-DM.''; PubMed Europe PMC Scholia
  63. Stern LJ, Brown JH, Jardetzky TS, Gorga JC, Urban RG, Strominger JL, Wiley DC.; ''Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide.''; PubMed Europe PMC Scholia
  64. Rocha N, Neefjes J.; ''MHC class II molecules on the move for successful antigen presentation.''; PubMed Europe PMC Scholia
  65. Kropshofer H, Arndt SO, Moldenhauer G, Hämmerling GJ, Vogt AB.; ''HLA-DM acts as a molecular chaperone and rescues empty HLA-DR molecules at lysosomal pH.''; PubMed Europe PMC Scholia
  66. Marks MS, Blum JS, Cresswell P.; ''Invariant chain trimers are sequestered in the rough endoplasmic reticulum in the absence of association with HLA class II antigens.''; PubMed Europe PMC Scholia
  67. Rodionov DG, Bakke O.; ''Medium chains of adaptor complexes AP-1 and AP-2 recognize leucine-based sorting signals from the invariant chain.''; PubMed Europe PMC Scholia
  68. Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ.; ''B lymphocytes secrete antigen-presenting vesicles.''; PubMed Europe PMC Scholia
  69. Schreiber KL, Bell MP, Huntoon CJ, Rajagopalan S, Brenner MB, McKean DJ.; ''Class II histocompatibility molecules associate with calnexin during assembly in the endoplasmic reticulum.''; PubMed Europe PMC Scholia
  70. Jensen PE.; ''Peptide binding and antigen presentation by class II histocompatibility glycoproteins.''; PubMed Europe PMC Scholia
  71. Hiltbold EM, Roche PA.; ''Trafficking of MHC class II molecules in the late secretory pathway.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
114894view16:40, 25 January 2021ReactomeTeamReactome version 75
113340view11:41, 2 November 2020ReactomeTeamReactome version 74
112550view15:51, 9 October 2020ReactomeTeamReactome version 73
101464view11:33, 1 November 2018ReactomeTeamreactome version 66
101002view21:12, 31 October 2018ReactomeTeamreactome version 65
100538view19:46, 31 October 2018ReactomeTeamreactome version 64
100085view16:31, 31 October 2018ReactomeTeamreactome version 63
99636view15:02, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93803view13:37, 16 August 2017ReactomeTeamreactome version 61
93341view11:20, 9 August 2017ReactomeTeamreactome version 61
87930view13:02, 25 July 2016RyanmillerOntology Term : 'signaling pathway pertinent to immunity' added !
87927view13:01, 25 July 2016RyanmillerOntology Term : 'signaling pathway' added !
87926view13:01, 25 July 2016RyanmillerOntology Term : 'PW:0000002' removed !
87925view13:01, 25 July 2016RyanmillerOntology Term : 'classic metabolic pathway' added !
86428view09:17, 11 July 2016ReactomeTeamreactome version 56
83080view09:53, 18 November 2015ReactomeTeamVersion54
81402view12:55, 21 August 2015ReactomeTeamVersion53
76872view08:14, 17 July 2014ReactomeTeamFixed remaining interactions
76577view11:55, 16 July 2014ReactomeTeamFixed remaining interactions
75910view09:56, 11 June 2014ReactomeTeamRe-fixing comment source
75610view10:46, 10 June 2014ReactomeTeamReactome 48 Update
74965view13:48, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74609view08:39, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
AP-1 Clathrin coated nonameric complexComplexREACT_123325 (Reactome)
AP-1 ComplexComplexREACT_11249 (Reactome)
AP1B1 ProteinQ10567 (Uniprot-TrEMBL)
AP1G1 ProteinO43747 (Uniprot-TrEMBL)
AP1M1 ProteinQ9BXS5 (Uniprot-TrEMBL)
AP1M2ProteinQ9Y6Q5 (Uniprot-TrEMBL)
AP1S1 ProteinP61966 (Uniprot-TrEMBL)
AP1S2 ProteinP56377 (Uniprot-TrEMBL)
AP1S3 ProteinQ96PC3 (Uniprot-TrEMBL)
AP2A1 ProteinO95782 (Uniprot-TrEMBL)
AP2A2ProteinO94973 (Uniprot-TrEMBL)
AP2B1 ProteinP63010 (Uniprot-TrEMBL)
AP2M1 ProteinQ96CW1 (Uniprot-TrEMBL)
AP2S1 ProteinP53680 (Uniprot-TrEMBL)
ARF1ProteinP84077 (Uniprot-TrEMBL)
ARP-1ProteinREACT_124999 (Reactome)
ATPMetaboliteCHEBI:15422 (ChEBI)
AntigenREACT_119525 (Reactome)
AntigenREACT_122664 (Reactome)
Arf1-GDPComplexREACT_11922 (Reactome)
Arf1-GTPComplexREACT_11673 (Reactome)
CANX ProteinP27824 (Uniprot-TrEMBL)
CANXProteinP27824 (Uniprot-TrEMBL)
CD74 ProteinP04233 (Uniprot-TrEMBL)
CD74ProteinP04233 (Uniprot-TrEMBL)
CENPE ProteinQ02224 (Uniprot-TrEMBL)
CLTA ProteinP09496 (Uniprot-TrEMBL)
CLTC-1 ProteinQ00610-1 (Uniprot-TrEMBL)
CLTC1-1 ProteinQ00610-1 (Uniprot-TrEMBL)
CathepsinProteinREACT_121862 (Reactome)
CathepsinProteinREACT_122689 (Reactome)
Clathrin TriskelionComplexREACT_15049 (Reactome)
Clathrin coated MHC class II alpha/beta/Ii nonamerComplexREACT_121490 (Reactome)
Clathrin coated MHC class II alpha/beta/Ii nonamerComplexREACT_123856 (Reactome)
Clathrin light chain ProteinP09496-1 (Uniprot-TrEMBL)
Clathrin-coated vesicleComplexREACT_125198 (Reactome)
Clathrin-coated vesicleComplexREACT_13103 (Reactome)
DCTN1 ProteinQ14203 (Uniprot-TrEMBL)
DCTN2 ProteinQ13561 (Uniprot-TrEMBL)
DCTN3ProteinO75935 (Uniprot-TrEMBL)
DCTN4ProteinQ9UJW0 (Uniprot-TrEMBL)
DCTN5 ProteinQ9BTE1 (Uniprot-TrEMBL)
DCTN6 ProteinO00399 (Uniprot-TrEMBL)
DYNC1H1 ProteinQ14204 (Uniprot-TrEMBL)
DYNC1I1 ProteinO14576 (Uniprot-TrEMBL)
DYNC1I2 ProteinQ13409 (Uniprot-TrEMBL)
DYNC1LI2 ProteinO43237 (Uniprot-TrEMBL)
DYNC2H1 ProteinQ8NCM8 (Uniprot-TrEMBL)
DYNC2LI1 ProteinQ8TCX1 (Uniprot-TrEMBL)
DYNLL1 ProteinP63167 (Uniprot-TrEMBL)
DYNLL2 ProteinQ96FJ2 (Uniprot-TrEMBL)
Dynamin-1/2/3ProteinREACT_22651 (Reactome)
DynaminProteinREACT_122824 (Reactome)
Dynein

Dynactin

microtubule		ComplexREACT_125410 (Reactome)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HLA II alpha chainProteinREACT_125425 (Reactome)
HLA II beta chainProteinREACT_123431 (Reactome)
HLA class II histocompatibility antigen, DM alpha chain precursor ProteinP28067 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DM beta chain precursor ProteinP28068 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DO alpha chain precursor ProteinP06340 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DO beta chain precursor ProteinP13765 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DP ProteinP04440 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DP alpha chain precursor ProteinP20036 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DQ ProteinP01906 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DQ ProteinP01909 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DQ ProteinP01920 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DQ beta 2 chain ProteinP05538 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor ProteinP01920 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DR alpha chain precursor ProteinP01903 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DR beta 4 chain ProteinP13762 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DR beta 5 chain ProteinQ30154 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DR-1 beta chain precursor ProteinP01912 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DRB1-1 beta chain ProteinP04229 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DRB1-10 beta chain ProteinQ30167 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DRB1-11 beta chain ProteinP20039 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DRB1-12 beta chain ProteinQ95IE3 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DRB1-13 beta chain ProteinQ5Y7A7 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DRB1-14 beta chain ProteinQ9GIY3 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DRB1-15 beta chain ProteinP01911 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DRB1-16 beta chain ProteinQ29974 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DRB1-4 beta chain ProteinP13760 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DRB1-7 beta chain ProteinP13761 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DRB1-8 beta chain ProteinQ30134 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DRB1-9 beta chain precursor ProteinQ9TQE0 (Uniprot-TrEMBL)
HLA class II histocompatibility antigen, DRB3-1 beta chain precursor ProteinP79483 (Uniprot-TrEMBL)
HLA-DM/HLA-DOProteinREACT_124165 (Reactome)
IFI30ProteinP13284 (Uniprot-TrEMBL)
Invariant chain trimerComplexREACT_124051 (Reactome)
KIF11 ProteinP52732 (Uniprot-TrEMBL)
KIF15 ProteinQ9NS87 (Uniprot-TrEMBL)
KIF18A ProteinQ8NI77 (Uniprot-TrEMBL)
KIF22 ProteinQ14807 (Uniprot-TrEMBL)
KIF26A ProteinQ9ULI4 (Uniprot-TrEMBL) KIF26A is atypical as it lacks ATPase activity.
KIF2A ProteinO00139 (Uniprot-TrEMBL)
KIF2B ProteinQ8N4N8 (Uniprot-TrEMBL)
KIF2C ProteinQ99661 (Uniprot-TrEMBL)
KIF3A ProteinQ9Y496 (Uniprot-TrEMBL)
KIF3B ProteinO15066 (Uniprot-TrEMBL)
KIF3C ProteinO14782 (Uniprot-TrEMBL)
KIF4A ProteinO95239 (Uniprot-TrEMBL)
KIF4B ProteinQ2VIQ3 (Uniprot-TrEMBL)
KIFAP3 ProteinQ92845 (Uniprot-TrEMBL)
Kinesins

Dynactin

microtubule		ComplexREACT_121653 (Reactome)
LGMNProteinQ99538 (Uniprot-TrEMBL)
MHC II CLIPComplexREACT_122680 (Reactome)
MHC II lip10 nonamerComplexREACT_124281 (Reactome)
MHC II lip22 nonamerComplexREACT_123870 (Reactome)
MHC II alpha beta heterodimerComplexREACT_123107 (Reactome)
MHC class II alpha/beta/Ii nonamerComplexREACT_122095 (Reactome)
MHC class II alpha/beta/Ii nonamerComplexREACT_123439 (Reactome)
MHC class II epitopesREACT_125085 (Reactome)
Nonameric complex in COPII vesicleComplexREACT_123192 (Reactome)
Nonameric complexComplexREACT_121584 (Reactome)
Nonameric complexComplexREACT_122724 (Reactome)
Nonameric complexComplexREACT_122768 (Reactome)
Nonameric complexComplexREACT_122861 (Reactome)
Nonameric complexComplexREACT_123017 (Reactome)
OSBPL1A ProteinQ9BXW6 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:18367 (ChEBI)
RAB7

RILP

ORP1L complex		ComplexREACT_124801 (Reactome)
RAB7A ProteinP51149 (Uniprot-TrEMBL)
RACGAP1 ProteinQ9H0H5 (Uniprot-TrEMBL)
RILP ProteinQ96NA2 (Uniprot-TrEMBL)
SAR1B ProteinQ9Y6B6 (Uniprot-TrEMBL)
SEC13 ProteinP55735 (Uniprot-TrEMBL)
SEC23A ProteinQ15436 (Uniprot-TrEMBL)
SEC24A ProteinO95486 (Uniprot-TrEMBL)
SEC24B ProteinO95487 (Uniprot-TrEMBL)
SEC24C ProteinP53992 (Uniprot-TrEMBL)
SEC24D ProteinO94855 (Uniprot-TrEMBL)
SEC31A ProteinO94979 (Uniprot-TrEMBL)
SH3GL2 ProteinQ99962 (Uniprot-TrEMBL)
SH3GL2ProteinQ99962 (Uniprot-TrEMBL)
SPTBN2ProteinO15020 (Uniprot-TrEMBL)
Sar1b

GTP Sec23p Sec24p Sec13p

Sec31p Complex		ComplexREACT_13165 (Reactome)
TGN-lysosome vesicle with nonameric complexComplexREACT_125234 (Reactome)
alpha beta dimer

Ii trimer

calnexin		ComplexREACT_123467 (Reactome)
peptide free MHC II HLA-DMComplexREACT_122875 (Reactome)
peptide loaded MHC class IIComplexREACT_123504 (Reactome)
peptide loaded MHC class IIComplexREACT_124034 (Reactome)
unfolded antigenREACT_124109 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowREACT_120995 (Reactome)
AP-1 Clathrin coated nonameric complexArrowREACT_121003 (Reactome)
AP-1 Clathrin coated nonameric complexREACT_120774 (Reactome)
AP-1 ComplexArrowREACT_120943 (Reactome)
AP-1 ComplexREACT_121003 (Reactome)
ARP-1ArrowREACT_120995 (Reactome)
ARP-1REACT_120995 (Reactome)
ATPREACT_120995 (Reactome)
Arf1-GDPArrowREACT_121003 (Reactome)
Arf1-GTPREACT_121003 (Reactome)
CANXArrowREACT_120846 (Reactome)
CANXREACT_121334 (Reactome)
CD74ArrowREACT_121161 (Reactome)
Cathepsinmim-catalysisREACT_120767 (Reactome)
Cathepsinmim-catalysisREACT_121107 (Reactome)
Cathepsinmim-catalysisREACT_121306 (Reactome)
Clathrin TriskelionArrowREACT_120943 (Reactome)
Clathrin TriskelionREACT_121003 (Reactome)
Clathrin coated MHC class II alpha/beta/Ii nonamerArrowREACT_120835 (Reactome)
Clathrin coated MHC class II alpha/beta/Ii nonamerREACT_120835 (Reactome)
Clathrin-coated vesicleArrowREACT_121177 (Reactome)
Clathrin-coated vesicleREACT_120771 (Reactome)
Dynamin-1/2/3mim-catalysisREACT_120835 (Reactome)
DynaminArrowREACT_120774 (Reactome)
DynaminREACT_121003 (Reactome)
Dynaminmim-catalysisREACT_120774 (Reactome)
Dynein

Dynactin

microtubule		ArrowREACT_120995 (Reactome)
Dynein

Dynactin

microtubule		REACT_120995 (Reactome)
GDPArrowREACT_120774 (Reactome)
GDPArrowREACT_120835 (Reactome)
GTPREACT_120774 (Reactome)
GTPREACT_120835 (Reactome)
H2OREACT_120835 (Reactome)
HLA II alpha chainREACT_121116 (Reactome)
HLA II beta chainREACT_121116 (Reactome)
HLA-DM/HLA-DOArrowREACT_120805 (Reactome)
HLA-DM/HLA-DOREACT_121161 (Reactome)
IFI30mim-catalysisREACT_121326 (Reactome)
Invariant chain trimerREACT_121334 (Reactome)
Kinesins

Dynactin

microtubule		ArrowREACT_120995 (Reactome)
Kinesins

Dynactin

microtubule		REACT_120995 (Reactome)
LGMNmim-catalysisREACT_121251 (Reactome)
MHC II CLIPREACT_121161 (Reactome)
MHC II alpha beta heterodimerREACT_120846 (Reactome)
MHC II alpha beta heterodimerREACT_121334 (Reactome)
MHC class II alpha/beta/Ii nonamerREACT_120771 (Reactome)
MHC class II epitopesREACT_120805 (Reactome)
Nonameric complexArrowREACT_120846 (Reactome)
Nonameric complexArrowREACT_120943 (Reactome)
Nonameric complexArrowREACT_121121 (Reactome)
Nonameric complexArrowREACT_121177 (Reactome)
Nonameric complexREACT_120802 (Reactome)
Nonameric complexREACT_121003 (Reactome)
PiArrowREACT_120774 (Reactome)
PiArrowREACT_120835 (Reactome)
PiArrowREACT_121003 (Reactome)
RAB7

RILP

ORP1L complex		ArrowREACT_120995 (Reactome)
RAB7

RILP

ORP1L complex		REACT_120995 (Reactome)
REACT_120767 (Reactome) Antigen processing and loading on to MHC class II molecules occurs in late endocytic/lysosomal vesicles, where epitopes which require extensive proteolytic processing are generated (Bryant & Ploegh 2003). These late endosome/lysosomal-like compartments are enriched in MHC II and are referred to as MIICs (MHC class II compartments) (Peters et al. 1991). A variety of lysosomal proteases like cathepsins S, D, B etc. and Asparaginyl endopeptidase (AEP) are suggested to be involved in the processing of antigens to generate CD4+ T cell epitopes (Deusing et al. 1998, Shi et al. 1999, Pluger et al. 2002, Watts et al. 2005). An initial cleavage by endopeptidases (AEP) would be necessary to unlock the antigen and allow further trimming of the ends by exopeptidases (Cathepsins). In the acidic environment of the lysosome, cathepsins are generally activated by autocatalytic cleavage of a propeptide which otherwise blocks the active site.
REACT_120768 (Reactome) The internalized nonameric complex passes through the endocytic pathway and finally reach the acidic late endosomal/lysosomal compartments, where the Ii component is progressively degraded by proteases. Proteolysis of Ii occurs through sequential cleavages from the lumenal (C-terminal) side, generating cleavage products of approximately 22 kDa (lip22) and 10 kDa (lip10), finally leaving only CLIP bound within the peptide binding groove of MHC II (Landsverk et al. 2009).
REACT_120771 (Reactome) Plasma membrane-associated nonameric complexes (MHC II alpha/beta/Ii complex) are rapidly internalized and delivered to late endosomes (LEs) and lysosomes. The dileucine-based signal present in the cytoplasmic tail of Ii is required for sorting of the nonameric MHC II-Ii complex from the plasma membrane to peptide loading compartments. These signals promote rapid internalization by recognising and binding to clathrin adaptor AP-2, a scaffolding-protein complex that brings together components of the vesicle-formation machinery. AP-2 is an essential component of an endocytic clathrin coat and participates in initiation of coat assembly. The critical role of AP2 in delivering MHC II:Ii complex to antigen processing compartments came from RNA interference studies targeting clathrin and AP2. The knockout of AP2 profoundly inhibited MHC II:Ii complex internalization and resulted in the accumulation of Ii at the surface (Dugast et al. 2005, McCormick et al. 2005).
REACT_120774 (Reactome) Budding vesicles loaded with the nonameric complex bud off from the TGN to reach the late-endosome/lysosome membrane.
REACT_120802 (Reactome) Immediately after assembly in the ER nonameric (alpha beta:Ii)3 complexes egress from ER, facilitated by the presence of Ii, and enter the Golgi complex (Wolf & Ploegh 1995, Geuze 1998). Incorrectly folded or oligomerized alpha, beta and Ii chains are retained in the ER and degraded. The Sec23/24-Sar1 pre-budding complex binds to the nonameric complex and then recruits Sec13/31 outer shell, which buds off from the membrane as a coat protein complex II (COPII) vesicle to be transported to the Golgi complex (Bickford et al. 2004).
REACT_120805 (Reactome) In the acidic compartments of MIICs the empty MHC II molecules are protected from unfolding and degradation by HLA-DM (DM). DM acts as a peptide editor, favouring the formation and presentation of long-lived MHC II peptide complexes on the surface of APCs. The intrinsic stability of a ligand determines whether a peptide is resistant or sensitive to DM-mediated release (Kropshofer et al. 1996, Weber et al. 1996). From X-ray structure analysis it is known that two types of forces contribute to the intrinsic stability of class II-peptide complexes: i) interactions of the anchor side chains of the peptides with specificity pockets of polymorphic residues of the peptide binding groove of MHC II and ii) hydrogen bonds between the peptide backbone and conserved residues of the peptide binding grooves (Stern et al. 1994, Kropshofer et al. 1999). Naturally-processed antigenic peptides 14-16 residues in length with many anchor residues and few destabilizing residues (glycine and proline) at non-anchor positions are the most resistant to DM-mediated release (Radrizzani et al. 1999, Kropshofer et al. 1999).
REACT_120835 (Reactome) MHC II:Ii complexes are internalized in to the endocytic clathrin coated-pit. Dynamin, the GTPase involved in the scission of clathrin-coated vesicles from plasma membrane is observed to be involved in the effective endocytosis of MHC II:Ii complexes. Wang et al, demonstrated that overexpression of a dominant-negative mutant of the GTPase dynamin resulted in the cell surface accumulation of MHC II:Ii complex, supporting that endocytosis is required for delivery to antigen processing compartments (Wang et al, 1997). However, another study using the same dynamin mutant generated opposite conclusions (Davidson, 1999). This discrepancy may be caused by differences in experimental set-up and in the levels of expression of the dynamin mutant and MHC II chains (Dugast et al, 2005).
REACT_120846 (Reactome) Progressive addition of two more preformed alpha beta dimers to the invariant chain trimer and alpha beta complex ((alpha beta)1:(Ii)3) forms the complete nonameric structure ((alpha beta:Ii)3). Calnexin then disassociates on egress of the nonameric complex from the ER.
REACT_120943 (Reactome) On reaching the late endosomes/lysosomes the TGN-lysosome vesicle uncoats and fuses with the lysosome to releases the MHC II nonameric complex.
REACT_120995 (Reactome) Once MHC class II-peptide complexes are formed, they must be transported back to the cell surface. It is unclear how this occurs. LEs/lysosomes with peptide loaded MHC II molecules may move in a bidirectional manner in a stop-and-go fashion along microtubules to the plasma membrane, driven by the activities of the oppositely-directed motor proteins dynein and kinesin (Wubbolts et al. 1996, 1999, Chow et al. 2002, Rocha & Neefjes 2007). Ultimately, LEs/lysosomes fuse to the plasma membrane delivering the MHC II-peptide complexes to the surface (Raposo et al. 1996, Rocha & Neefjes 2007). RAB7-GTP present on LEs/lysosome membrane interacts with Rab7-interacting lysosomal protein (RILP) and oxysterol-binding protein-related protein 1L (ORP1L) to form a tripartite RILP-Rab7-ORP1L complex. RILP binds to the p150 dynactin subunit to recruit the dynein or kinesin motor proteins. ORP1L recruits this complex to betaIII spectrin domains, which appears to be critical for dynein motor activation and transport of LEs/lysosome vesicles to the cell periphery (Johansson et al. 2007, Rocha & Neefjes 2008).
REACT_121003 (Reactome) The trans-Golgi network (TGN) is the sorting and package centre for trafficking cargo to the endoplasmic reticulum, plasma membrane and endosomes. Signal peptides determine the sorting and trafficking of proteins to the endosomal-lysosomal pathway or to the cell surface. The main signals that mediate targeting of MHC-II molecules to the endocytic pathway are two dileucine-based motifs, Leu23-Ile24 and Pro31-Leu33 present in the short cytoplasmic tail of Ii (Odorizzi et al. 1994). These motifs bind both the adaptor proteins AP-1 and AP-2, which are components of clathrin coats associated with the TGN/endosomes and the plasma membrane, respectively (McCormick et al. 2005). The precise pathway of class II:Ii complex trafficking from TGN to endocytic pathway is not well understood. In one view MHC II:Ii complexes directly traffic from the TGN to lysosomes, possibly using AP-1 dependent endocytic vesicles (Peters et al. 1991, Amigorena et al. 1994). Alternatively trafficking occurs via transient expression on the cell surface followed by rapid internalization and delivery to endocytic compartments. Early immunoelectron microscopy data has shown the presence of MHC class II:Ii complex molecules primarily in TGN and lysosomes (Peters et al. 1991, Hiltbold & Roche 2002). This theory was further supported by a study examining the trafficking of sulphate-tagged class II molecules, which concluded that the rapid appearance of these molecules in lysosomes was consistent with their direct transport from the TGN to lysosomes (Hiltbold & Roche 2002, Davidson 1999). The transport of cargo MHC II:Ii complexes from the TGN to lysosomes may be mediated by small TGN vesicles coated with AP-1 and clathrin. The di-leucine-based sorting signal in the Ii cytoplasmic chain recruits AP-1 and clathrin from cytosol to TGN to form AP-1 clathrin-coated TGN-derived vesicles. This process is regulated by the small GTPase ARF-1 (Salamero et al. 1996).
REACT_121019 (Reactome) The newly formed MHC II-Ii complex exits the TGN and ultimately is delivered to late-endosome/lysosome compartments. A proportion of the nonameric complex traffics directly from the TGN to these compartments, while a substantial population follow the indirect pathway involving transport from the TGN to the plasma membrane, followed by endocytic delivery to early endosomes, late endosomes, and finally lysosomes (McCormick et al. 2005). Transport carrier vesicles may traffic the cargo MHC II-Ii complex from the TGN to the plasma membrane.
REACT_121063 (Reactome) On reaching the cell surface, transport carrier vesicles insert the cargo MHC II:Ii complex into the plasma membrane.
REACT_121107 (Reactome) The lip10 fragments bound in the nonameric complex are processed leaving only the CLIP fragment (81-105) bound to the MHC II peptide binding groove. Three cysteine proteases have been shown to be capable of digesting lip10, each with a different expression pattern among different APC. Cathepsin (Cat) S digests Ii in B cells and dendritic cells, thymic epithelial cells use Cat L and Cat L, while Cat S and F are active in macrophages (Villadangos, 2001; Bryant et al, 2002). Cat S appears to be the major enzyme involved as demonstrated by the use of specific inhibitors and of knockout experiments (Stumptner-Cuvelette et al. 2002). Following lip10 digestion, the MHC-like molecule HLA-DM induces the exchange of CLIP fragment for a highly diverse array of antigens (Denzin & Cresswell. 1995).
REACT_121116 (Reactome) MHC II alpha and beta chains translocate to the ER and associate noncovalently to form an alpha beta heterodimer (Roche et al. 1991). This heterodimer then associates with a preformed invariant (Ii) chain trimer.
REACT_121121 (Reactome) The COPII vesicle uncoats and fuses with the cis-Golgi, releasing the MHC II:Ii complex into the Golgi.
REACT_121145 (Reactome) MHC II typically presents antigens derived from exogenous proteins internalized by APCs such as macrophages, B cells or dendritic cells. Different types of antigen use different routes of internalization. Endocytosis may be specific, mediated by a range of receptors expressed on APC, or may occur by nonspecific mechanisms such as phagocytosis, macropinocytosis or autophagy. Antigens are first loaded into endocytic vesicles and progress along the early endosomes (EE)-late endosomes (LE) lysosomal axis. Antigens are exposed to increasingly acidic, more denaturing and proteolytic conditions (Doherty & McMahon 2009, Underhill & Ozinsky 2002).
REACT_121161 (Reactome) To gain the capacity to activate antigen-specific T cells, MHC class II-associated CLIP must be exchanged for an antigenic peptide (Kropshofer et al. 1999). There are two CLIP variants in humans: CLIP(long) with 21-26 residues, and CLIP(short) with 14-19 residues. CLIP(long) disassociates rapidly from HLA-DR molecules at endosomal/lysosomal pH, whereas CLIP(short) displays a lower off-rate. The N-terminal 9 residues of CLIP (81-89) facilitate its rapid release (Urban et al. 1994, Kropshofer et al. 1995a, Kropshofer et al. 1995b). The non-classical MHC class II molecule HLA-DM (DM) functions as a mediator of peptide exchange by accelerating the removal of CLIP. DM mediated peptide release involves a direct interaction between DM and the class II molecule. In addition to peptide release, DM also acts as a chaperone for MHC class II molecules in endosomal/lysosomal compartments. It stabilizes the peptide-receptive empty MHC II molecules and prevents them from unfolding and also favors the generation of high-stability peptide-MHC class II complexes by promoting release of low-stability peptide ligands (Kropshofer et al. 1999, Kropshofer et al. 1997). Another non-classical MHC II molecule HLA-DO (DO), only expressed in B-cells and thymic epithelial cells, binds tightly to DM modulating DM activity both negatively and positively, depending on the amount of DO present in an APC. Heterotypic DR-DM-DO complexes are receptive for peptide loading, in these complexes DO does not appear to be inhibitory (Denzin et al. 1997, Kropshofer et al. 1998, Kropshofer et al. 1999).
REACT_121177 (Reactome) MHC II:Ii complexes bound to clathrin-coated vesicles rapidly fuse with endosomes.
REACT_121251 (Reactome) Within acidic endocytic compartments Ii is proteolytically cleaved, ultimately freeing the class II peptide-binding groove for loading of antigenic peptides. Ii is degraded in a stepwise manner by a combination of aspartyl and cysteine proteases, following a well defined path with intermediates lip22, lip10 and finally CLIP. The initial Ii cleavage has been ascribed to leupeptin-insensitive cysteine or aspartic proteases, which include aspartyl protease and asparagine endopeptidase (AEP) (Maric et al. 1994, Manoury et al. 2003, Costantino et al. 2008). These proteases generate 22 kDa fragments of Ii (lip22). The trimerization domain of human Ii (residues 134-208) has three possible AEP cleavage sites, Asn148, 165 and 171. Asn171, located at the C-terminal end of helix B, is the demonstrated cleavage site for AEP (Manoury et al. 2003, Jasanoff et al. 1998). This cleavage eliminates the C-terminal trimerization domain of Ii, which causes disassociation of the (MHC II:Ii)3 nonamer and exposes new cleavage sites in the MHC II:lip22 trimers (Villadangos et al. 1999, Guillaume et al. 2008). The residue numbering of Ii given above is based on Uniprot isoform 1.
REACT_121306 (Reactome) The cleavage of lip22 occurs in residues 115-125, closer to the C-terminus than CLIP (residues 81-105). The resulting lip10 fragment is approximately 100 residues long and extends just through the C-terminus of the Ii CLIP. The proteases responsible for generating lip10 in vivo are not determined. Cysteine proteases like cathepsin S (CatS) are capable of degrading lip22 to lip10 (Bania et al. 2003) but in the presence of LHVS, an inhibitor of CatS, lip22 degradation is still observed, suggesting that other proteases are involved (Villadangos et al. 1997), possibly aspartic proteinases such as cathepsins D and E (Kageyama et al. 1996). The degradation of lip22 may depend on cell type (Bania et al. 2003). The lip22 and lip10 intermediate forms are still maintained as a nonameric complex due to the existence of the last trimerisation domain in the transmembrane region.
REACT_121309 (Reactome) Nonameric MHC II:Ii complex move through the various cisternae to reach the trans-golgi network (TGN), a tubulo-vesicular organelle located at the trans-face of Golgi stacks. From the TGN, MHC II:Ii complexes are targeted to the endocytic pathway for peptide loading.
REACT_121326 (Reactome) MHC class II epitopes require protein denaturation and removal of intra- and inter-chain disulphide bonds prior to proteolysis. The lysosomal thiol reductase gamma-IFN-inducible lysosomal thiol reductase (GILT) has been shown to facilitate MHC class II-restricted antigen (Ag) processing by breaking disulphide bonds. GILT is constitutively expressed in APCs. The reduction of disulphide bonds by mature GILT is optimal at acidic pH (Hastings et al. 2006, Arunachalam et al. 2000).
REACT_121334 (Reactome) MHC II alpha beta dimers associate with a third polypeptide, the invariant chain (Ii), required for class II molecules to reach the endocytic pathway (Roche et al. 1991). The interaction of Ii with the MHC II alpha beta dimer serves multiple functions. It plays a role in assembly, folding, egress from the ER and transport through the Golgi. Ii exists as a trimer; residues 163-183 of the Ii lumenal domain are involved in covalent cross-linking. Residues 96-104 are critical for association with class II alpha beta dimers (Bijlmakers et al. 1994, Freisewinkel et al. 1993). Residues 89-104 known as CLIP (Class II-associated invariant chain peptide) are the part of the Ii chain that binds antigen binding MHC class II groove, remaining bound until the MHC receptor is completely assembled. This CLIP domain prevents the premature binding of self-peptide fragments present in ER prior to MHC II localization within the endosomal compartment. The ER-resident chaperone protein calnexin rapidly associates with newly synthesized alpha, beta and invariant chains, and remains associated until the final nonamer assembly. The stoichiometry of calnexin in this interaction and the dynamics of association-dissociation are not known. Calnexin may stabilize the free class II chains and regulate their intracellular transport by facilitating the production of transport competent molecules out of the ER (Anderson & Cresswell 1994, Schreiber et al. 1995).
SH3GL2ArrowREACT_121177 (Reactome)
SH3GL2REACT_120835 (Reactome)
SPTBN2ArrowREACT_120995 (Reactome)
SPTBN2REACT_120995 (Reactome)
Sar1b

GTP Sec23p Sec24p Sec13p

Sec31p Complex		ArrowREACT_121121 (Reactome)
Sar1b

GTP Sec23p Sec24p Sec13p

Sec31p Complex		REACT_120802 (Reactome)
TGN-lysosome vesicle with nonameric complexArrowREACT_120774 (Reactome)
alpha beta dimer

Ii trimer

calnexin		REACT_120846 (Reactome)
peptide free MHC II HLA-DMArrowREACT_121161 (Reactome)
peptide free MHC II HLA-DMREACT_120805 (Reactome)
peptide loaded MHC class IIArrowREACT_120805 (Reactome)
peptide loaded MHC class IIArrowREACT_120995 (Reactome)
peptide loaded MHC class IIREACT_120995 (Reactome)
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