MHC class II antigen presentation (Homo sapiens)

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27, 29, 37, 44, 6718, 23, 24, 26, 41...3, 20, 45, 4617, 32, 34, 682, 9, 12, 28, 34...2, 472, 6, 1627, 33, 51, 54344, 7, 48, 612, 9, 12, 28, 34...1913, 31, 50, 55-57, 602, 21, 32, 365, 48, 611, 10, 25, 43, 51...8, 21, 3211, 18, 38, 39, 4215, 22, 30, 59, 642, 66, 1440, 492, 9, 12, 28, 35...17, 3258, 62325, 48, 615, 48, 53, 61, 69...Golgi membranetransport vesiclecytosoltrans-Golgi network membranelysosomal lumenendoplasmic reticulum lumenendocytic vesicleCOPII-coated ER to Golgi transport vesicleclathrin-coated endocytic vesicleAP1B1 HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-4 beta chain CD74 HLA class II histocompatibility antigen, DR beta 5 chain DCTN6 Arf1-GDPHLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DR beta 4 chain ACTR1B PiHLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-13 beta chain DCTN5 Clathrin light chain HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain CTSB(80-333) HLA class II histocompatibility antigen, DRB1-12 beta chain SEC31A HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DQ CLTC HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain CD74 HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DP CTSD(65-412) HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain AP2S1 HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DP alpha chain precursor DNM2 DCTN2 HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DQ MHC II:lip22 nonamerAP1S2 HLA class II histocompatibility antigen, DRB1-10 beta chain CD74(81-104) HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DQ CAPZA2 HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DO alpha chain precursor HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DR beta 5 chain CANX 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, DQB1*0602 beta chain precursor CLTA HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-1 beta chain DNM3 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 HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DRB1-9 beta chain precursor DCTN5 SEC23A HLA class II histocompatibility antigen, DRB3-1 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, DR beta 5 chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-15 beta chain AP2A1 HLA class II histocompatibility antigen, DP alpha chain precursor CTSD(65-412) HLA class II histocompatibility antigen, DQ beta 2 chain SEC31A KIF5B HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor CD74 KIF3B HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor DCTN3 RAB7:RILP:ORP1LcomplexHLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DRB1-1 beta chain CANX Dynein:Dynactin:microtubuleHLA class II histocompatibility antigen, DQ peptide free MHCII:HLA-DMHLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-13 beta chain AP1S1 CTSA(29-480) HLA class II histocompatibility antigen, DRB3-1 beta chain precursor AP2S1 HLA class II histocompatibility antigen, DRB1-16 beta chain KLC2 HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-7 beta chain MHC II alpha betaheterodimerCathepsinHLA class II histocompatibility antigen, DP HLA-DM/HLA-DOHLA class II histocompatibility antigen, DR beta 4 chain KIFAP3 Nonameric complex inCOPII vesicleHLA class II histocompatibility antigen, DRB1-14 beta chain DYNC1I1 HLA class II histocompatibility antigen, DRB1-9 beta chain precursor CD74 HLA class II histocompatibility antigen, DRB3-1 beta chain precursor CTSL1(114-288) HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DQ beta 2 chain CTSL2 DNM2 HLA class II histocompatibility antigen, DM beta chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DQ Microtubule protofilament IFI30HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain CLTC AP1B1 HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-8 beta chain SAR1B HLA class II histocompatibility antigen, DR alpha chain precursor SEC24C HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-4 beta chain GTP MHC class IIalpha/beta/IinonamerSEC13 CTSK AP1M2 HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor CD74(1-117) Clathrin light chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DQ beta 2 chain ACTR10 HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DR alpha chain precursor CTSE(54-401) HLA class II histocompatibility antigen, DRB1-16 beta chain AP1B1 HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-9 beta chain precursor SEC24A HLA class II histocompatibility antigen, DP AP1G1 HLA class II histocompatibility antigen, DQ CLTC-1 HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DR beta 4 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, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR alpha chain precursor CD74 AP2A2(1-939) HLA class II histocompatibility antigen, DRB1-10 beta chain PiHLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain AntigenHLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA 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, DRB1-16 beta chain KIF26A HLA class II histocompatibility antigen, DRB1-1 beta chain 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 SEC24D HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-13 beta chain GTP HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-4 beta chain AP2A2(1-939) CTSO LAG3HLA class II histocompatibility antigen, DQ beta 2 chain AP2A2(1-939) HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DRB1-4 beta chain ACTR1A MHC class IIepitopesHLA class II histocompatibility antigen, DRB1-11 beta chain 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 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, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor ACTR1A HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DR beta 4 chain AP1S1 HLA class II histocompatibility antigen, DRB1-11 beta chain unfolded antigenHLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DQ AP1S1 HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DR 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, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DR-1 beta chain precursor KIF23 HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB3-1 beta chain precursor AP1M1 HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB1-9 beta chain precursor CTSL2 HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-1 beta chain CANXLGMNHLA class II histocompatibility antigen, DRB1-11 beta chain CD74 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, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-14 beta chain SAR1B HLA class II histocompatibility antigen, DQ beta 2 chain HLA II beta chainHLA class II histocompatibility antigen, DQ 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, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-16 beta chain CTSD(65-412) HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor CD74 GTPpeptide loaded MHCclass IIHLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DRB3-1 beta chain precursor GDPHLA class II histocompatibility antigen, DR beta 5 chain GTP HLA class II histocompatibility antigen, DRB3-1 beta chain precursor Arf1-GTPCathepsinHLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DQ AP1S2 DNM1 SH3GL2SEC24B CTSB(80-333) HLA class II histocompatibility antigen, DQ SH3GL2HLA class II histocompatibility antigen, DR beta 5 chain CD74 HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DQ Nonameric complexHLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor AP2M1 HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-11 beta chain AP1G1 HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain DNM3 HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain SEC24A DYNLL2 Nonameric complexHLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain DNM3 SEC24D CTSL1(114-288) HLA class II histocompatibility antigen, DR beta 5 chain CD74(1-176) HLA class II histocompatibility antigen, DR alpha chain precursor CD74 HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-4 beta chain AP1M1 HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DR alpha 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, DRB1-7 beta chain HLA class II histocompatibility antigen, DP CD74(81-104)HLA class II histocompatibility antigen, DR-1 beta chain precursor AP1G1 AP1M1 HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor CAPZA2 HLA class II histocompatibility antigen, DRB1-4 beta chain MHC class II epitopes HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB1-7 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, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain Clathrin light chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-13 beta chain MHC class IIalpha/beta dimerHLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DQ MHC II:CLIPHLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor CTSS HLA class II histocompatibility antigen, DQ Clathrin coated MHCclass IIalpha/beta/IinonamerHLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-14 beta chain SEC24B CTSK HLA class II histocompatibility antigen, DRB1-12 beta chain DYNC1H1 HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor AP1S3 HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain CTSF CLTC-1 HLA class II histocompatibility antigen, DRB1-10 beta chain KIF18A HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB3-1 beta chain precursor RACGAP1 DCTN4 CLTC-1 HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DR-1 beta chain precursor CTSH(116-335) HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-7 beta chain CD74 HLA class II histocompatibility antigen, DRB1-4 beta chain AP1S2 CLTA CTSC(25-134) HLA class II histocompatibility antigen, DRB1-4 beta chain H2OGTP HLA class II histocompatibility antigen, DQ KIF15 HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DQ beta 2 chain CTSE(54-401) CD74 HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor GTPHLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DRB1-1 beta chain KIF3A HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain CathepsinHLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DP alpha chain precursor CLTA Clathrin:AP-2complexHLA class II histocompatibility antigen, DQ CTSS HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-16 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, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain Clathrin TriskelionHLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DQ CTSC(25-134) HLA class II histocompatibility antigen, DR beta 4 chain CTSH(116-335) HLA class II histocompatibility antigen, DRB1-14 beta chain RAB7A RILP HLA class II histocompatibility antigen, DRB1-14 beta chain CTSS HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-14 beta 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, DQ KLC3 DCTN2 AP2B1 HLA class II histocompatibility antigen, DRB3-1 beta chain precursor CENPE HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-13 beta chain ATPHLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-16 beta chain CD74 HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DP alpha chain precursor CTSH(116-335) CLTC HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain DYNC1I2 HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain LAG3 ACTR1A 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 KIF5A HLA class II histocompatibility antigen, DR-1 beta chain precursor AP2M1 HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-10 beta chain CLTC HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain AP1S2 Clathrin light chain HLA class II histocompatibility antigen, DQ CTSA(29-480) HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DP Clathrin:AP2 complexAP1M2 SEC23A 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, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-10 beta chain MHC II:lip10 nonamerHLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DR alpha chain precursor DYNLL1 CTSE(54-401) HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-12 beta chain SEC13 HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-16 beta chain DYNC1LI2 AP1M2 CAPZA3 HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DM alpha chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DQ DCTN3 DCTN6 GTP HLA class II histocompatibility antigen, DRB1-10 beta 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, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor peptide loaded MHCclass IIADPHLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DR alpha chain precursor OSBPL1A HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain Kinesin-13 dimers HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain TGN-lysosome vesiclewith nonamericcomplexHLA class II histocompatibility antigen, DRB1-13 beta chain Dynamin-1/2/3HLA class II histocompatibility antigen, DRB1-9 beta chain precursor DCTN1 HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-8 beta chain CTSB(80-333) HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-16 beta chain AntigenHLA class II histocompatibility antigen, DP CD74 HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR beta 4 chain Nonameric complexHLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB3-1 beta chain precursor ARP-1HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DQ GDPHLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DP alpha 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, DRB1-10 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor CTSF CLTA AP2A1 HLA class II histocompatibility antigen, DRB1-10 beta chain CTSO HLA class II histocompatibility antigen, DRB1-16 beta chain CTSC(25-134) HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor AP1S3 HLA class II histocompatibility antigen, DRB1-9 beta chain precursor CAPZB GDP HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DP MHC II alpha betaheterodimerHLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB1-16 beta chain Invariant chaintrimerHLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor DNM3 HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DQ 2xMHC II alpha betaheterodimer:alphabeta dimer:IitrimerMHC class IIalpha/beta/IinonamerHLA class II histocompatibility antigen, DRB1-11 beta chain DynaminHLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor AP2B1 HLA class II histocompatibility antigen, DR beta 5 chain CAPZA1 HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DP alpha chain precursor CTSF HLA class II histocompatibility antigen, DRB1-1 beta chain CLTC-1 HLA class II histocompatibility antigen, DQ Nonameric complexCOPIIHLA class II histocompatibility antigen, DQ CTSL2 HLA class II histocompatibility antigen, DRB1-10 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, DRB1-1 beta chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DR beta 4 chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DQ 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, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor HLA class II histocompatibility antigen, DP AP1G1 CD74 KLC1 Chromokinesin dimers AP1S3 HLA class II histocompatibility antigen, DRB1-1 beta chain ARF1 AP2S1 HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain 2xMHC II alpha betaheterodimer:alphabeta dimer:Iitrimer:calnexinAP2A1 HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DQ AP1S1 AP-1Complex:Arf1-GTP:Clathrin Triskelion:Nonameric complexHLA class II histocompatibility antigen, DR alpha chain precursor MHC class II epitopes HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-12 beta chain alpha beta dimer:Iitrimer:calnexinHLA class II histocompatibility antigen, DRB1-14 beta chain AP2B1 HLA class II histocompatibility antigen, DR beta 5 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, DRB1-1 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain DNM2 HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-1 beta chain DCTN4 HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB1-12 beta chain ARF1 HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DQ 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, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor DCTN1 HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB3-1 beta chain precursor CAPZA3 ACTR10 HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DRB1-4 beta chain AP1S3 AP2B1 HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain CAPZB HLA class II histocompatibility antigen, DR alpha chain precursor HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DR alpha chain precursor DNM2 AP-1 ComplexHLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DR-1 beta chain precursor PiMicrotubule protofilament HLA class II histocompatibility antigen, DP alpha chain precursor AP1B1 HLA class II histocompatibility antigen, DP alpha chain precursor DNM1 HLA class II histocompatibility antigen, DM alpha chain precursor HLA class II histocompatibility antigen, DRB1-16 beta chain HLA class II histocompatibility antigen, DP alpha chain precursor CTSA(29-480) Clathrin coated MHCclass IIalpha/beta/IinonamerHLA class II histocompatibility antigen, DM beta chain precursor HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DQ AP2M1 HLA class II histocompatibility antigen, DQ beta 2 chain CTSL1(114-288) HLA class II histocompatibility antigen, DRB3-1 beta chain precursor CD74 LAG3:MHC IIHLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DQ beta 2 chain HLA II alpha chainSEC24C HLA class II histocompatibility antigen, DRB1-13 beta chain CD74 HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-1 beta chain AP1M1 HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DR beta 4 chain Kinesins:Dynactin:microtubuleHLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain HLA class II histocompatibility antigen, DR beta 5 chain AP2M1 HLA class II histocompatibility antigen, DR-1 beta chain precursor AP2A1 HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DP AP1M2 HLA class II histocompatibility antigen, DRB1-1 beta chain AP2A2(1-939) HLA class II histocompatibility antigen, DO beta chain precursor CTSO KLC4 AP2S1 CD74 HLA class II histocompatibility antigen, DRB1-10 beta chain ARF1 HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-14 beta chain DNM1 HLA class II histocompatibility antigen, DRB1-4 beta chain HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor AP-1 Clathrin coatednonameric complexKIF20A Nonameric complexHLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DO 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, DP alpha chain precursor HLA class II histocompatibility antigen, DRB1-1 beta chain HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-15 beta chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-13 beta chain HLA class II histocompatibility antigen, DR-1 beta chain precursor HLA class II histocompatibility antigen, DRB1-12 beta chain HLA class II histocompatibility antigen, DRB1-4 beta chain SPTBN2HLA class II histocompatibility antigen, DQ beta 2 chain DYNC1LI1 KIF3C HLA class II histocompatibility antigen, DQ Kinesin-3 dimers HLA class II histocompatibility antigen, DR beta 5 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, DR-1 beta chain precursor HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DP HLA class II histocompatibility antigen, DRB1-1 beta chain KIF11 HLA class II histocompatibility antigen, DRB1-8 beta chain HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DRB1-11 beta chain SH3GL2 HLA class II histocompatibility antigen, DRB1-11 beta chain HLA class II histocompatibility antigen, DRB1-9 beta chain precursor HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DQB1*0602 beta chain precursor HLA class II histocompatibility antigen, DQ HLA class II histocompatibility antigen, DQ beta 2 chain HLA class II histocompatibility antigen, DRB1-7 beta chain HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DR beta 5 chain CAPZA1 HLA class II histocompatibility antigen, DR beta 5 chain HLA class II histocompatibility antigen, DR beta 4 chain CTSK DNM1 HLA class II histocompatibility antigen, DRB1-10 beta chain HLA class II histocompatibility antigen, DO alpha chain precursor HLA class II histocompatibility antigen, DRB1-1 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). View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 2132295
Reactome-version 
Reactome version: 73
Reactome Author 
Reactome Author: Garapati, Phani Vijay

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Bibliography

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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

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NameTypeDatabase referenceComment
2xMHC II alpha beta

heterodimer:alpha beta dimer:Ii

trimer:calnexin
ComplexR-HSA-8951502 (Reactome)
2xMHC II alpha beta

heterodimer:alpha beta dimer:Ii

trimer
ComplexR-HSA-8980062 (Reactome)
ACTR10 ProteinQ9NZ32 (Uniprot-TrEMBL)
ACTR1A ProteinP61163 (Uniprot-TrEMBL)
ACTR1B ProteinP42025 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:456216 (ChEBI)
AP-1 Complex:Arf1-GTP:Clathrin Triskelion:Nonameric complexComplexR-HSA-8951497 (Reactome)
AP-1 Clathrin coated nonameric complexComplexR-HSA-2130552 (Reactome)
AP-1 ComplexComplexR-HSA-167717 (Reactome)
AP1B1 ProteinQ10567 (Uniprot-TrEMBL)
AP1G1 ProteinO43747 (Uniprot-TrEMBL)
AP1M1 ProteinQ9BXS5 (Uniprot-TrEMBL)
AP1M2 ProteinQ9Y6Q5 (Uniprot-TrEMBL)
AP1S1 ProteinP61966 (Uniprot-TrEMBL)
AP1S2 ProteinP56377 (Uniprot-TrEMBL)
AP1S3 ProteinQ96PC3 (Uniprot-TrEMBL)
AP2A1 ProteinO95782 (Uniprot-TrEMBL)
AP2A2(1-939) ProteinO94973 (Uniprot-TrEMBL)
AP2B1 ProteinP63010 (Uniprot-TrEMBL)
AP2M1 ProteinQ96CW1 (Uniprot-TrEMBL)
AP2S1 ProteinP53680 (Uniprot-TrEMBL)
ARF1 ProteinP84077 (Uniprot-TrEMBL)
ARP-1ComplexR-HSA-2228747 (Reactome)
ATPMetaboliteCHEBI:30616 (ChEBI)
AntigenR-ALL-2213221 (Reactome)
AntigenR-ALL-983667 (Reactome)
Arf1-GDPComplexR-HSA-201340 (Reactome)
Arf1-GTPComplexR-HSA-199981 (Reactome)
CANX ProteinP27824 (Uniprot-TrEMBL)
CANXProteinP27824 (Uniprot-TrEMBL)
CAPZA1 ProteinP52907 (Uniprot-TrEMBL)
CAPZA2 ProteinP47755 (Uniprot-TrEMBL)
CAPZA3 ProteinQ96KX2 (Uniprot-TrEMBL)
CAPZB ProteinP47756 (Uniprot-TrEMBL)
CD74 ProteinP04233 (Uniprot-TrEMBL)
CD74(1-117) ProteinP04233 (Uniprot-TrEMBL)
CD74(1-176) ProteinP04233 (Uniprot-TrEMBL)
CD74(81-104) ProteinP04233 (Uniprot-TrEMBL)
CD74(81-104)ProteinP04233 (Uniprot-TrEMBL)
CENPE ProteinQ02224 (Uniprot-TrEMBL)
CLTA ProteinP09496 (Uniprot-TrEMBL)
CLTC ProteinQ00610 (Uniprot-TrEMBL)
CLTC-1 ProteinQ00610-1 (Uniprot-TrEMBL)
COPIIComplexR-HSA-203999 (Reactome)
CTSA(29-480) ProteinP10619 (Uniprot-TrEMBL)
CTSB(80-333) ProteinP07858 (Uniprot-TrEMBL)
CTSC(25-134) ProteinP53634 (Uniprot-TrEMBL)
CTSD(65-412) ProteinP07339 (Uniprot-TrEMBL)
CTSE(54-401) ProteinP14091 (Uniprot-TrEMBL)
CTSF ProteinQ9UBX1 (Uniprot-TrEMBL)
CTSH(116-335) ProteinP09668 (Uniprot-TrEMBL)
CTSK ProteinP43235 (Uniprot-TrEMBL)
CTSL1(114-288) ProteinP07711 (Uniprot-TrEMBL)
CTSL2 ProteinO60911 (Uniprot-TrEMBL)
CTSO ProteinP43234 (Uniprot-TrEMBL)
CTSS ProteinP25774 (Uniprot-TrEMBL)
CathepsinComplexR-HSA-2130544 (Reactome)
CathepsinComplexR-HSA-2130682 (Reactome)
Chromokinesin dimers R-HSA-984722 (Reactome)
Clathrin TriskelionComplexR-HSA-350827 (Reactome)
Clathrin coated MHC

class II alpha/beta/Ii

nonamer
ComplexR-HSA-2130309 (Reactome)
Clathrin coated MHC

class II alpha/beta/Ii

nonamer
ComplexR-HSA-2130331 (Reactome)
Clathrin light chain ProteinP09496-1 (Uniprot-TrEMBL)
Clathrin:AP-2 complexComplexR-HSA-177505 (Reactome)
Clathrin:AP2 complexComplexR-HSA-2130671 (Reactome)
DCTN1 ProteinQ14203 (Uniprot-TrEMBL)
DCTN2 ProteinQ13561 (Uniprot-TrEMBL)
DCTN3 ProteinO75935 (Uniprot-TrEMBL)
DCTN4 ProteinQ9UJW0 (Uniprot-TrEMBL)
DCTN5 ProteinQ9BTE1 (Uniprot-TrEMBL)
DCTN6 ProteinO00399 (Uniprot-TrEMBL)
DNM1 ProteinQ05193 (Uniprot-TrEMBL)
DNM2 ProteinP50570 (Uniprot-TrEMBL)
DNM3 ProteinQ9UQ16 (Uniprot-TrEMBL)
DYNC1H1 ProteinQ14204 (Uniprot-TrEMBL)
DYNC1I1 ProteinO14576 (Uniprot-TrEMBL)
DYNC1I2 ProteinQ13409 (Uniprot-TrEMBL)
DYNC1LI1 ProteinQ9Y6G9 (Uniprot-TrEMBL)
DYNC1LI2 ProteinO43237 (Uniprot-TrEMBL)
DYNLL1 ProteinP63167 (Uniprot-TrEMBL)
DYNLL2 ProteinQ96FJ2 (Uniprot-TrEMBL)
Dynamin-1/2/3ComplexR-HSA-446847 (Reactome)
DynaminComplexR-HSA-2213185 (Reactome)
Dynein:Dynactin:microtubuleComplexR-HSA-2029135 (Reactome)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HLA II alpha chainComplexR-HSA-2130718 (Reactome)
HLA II beta chainComplexR-HSA-2130672 (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-DOComplexR-HSA-2213230 (Reactome)
IFI30ProteinP13284 (Uniprot-TrEMBL)
Invariant chain trimerComplexR-HSA-2130599 (Reactome)
KIF11 ProteinP52732 (Uniprot-TrEMBL)
KIF15 ProteinQ9NS87 (Uniprot-TrEMBL)
KIF18A ProteinQ8NI77 (Uniprot-TrEMBL)
KIF20A ProteinO95235 (Uniprot-TrEMBL)
KIF23 ProteinQ02241 (Uniprot-TrEMBL)
KIF26A ProteinQ9ULI4 (Uniprot-TrEMBL) KIF26A is atypical as it lacks ATPase activity.
KIF3A ProteinQ9Y496 (Uniprot-TrEMBL)
KIF3B ProteinO15066 (Uniprot-TrEMBL)
KIF3C ProteinO14782 (Uniprot-TrEMBL)
KIF5A ProteinQ12840 (Uniprot-TrEMBL)
KIF5B ProteinP33176 (Uniprot-TrEMBL)
KIFAP3 ProteinQ92845 (Uniprot-TrEMBL)
KLC1 ProteinQ07866 (Uniprot-TrEMBL)
KLC2 ProteinQ9H0B6 (Uniprot-TrEMBL)
KLC3 ProteinQ6P597 (Uniprot-TrEMBL)
KLC4 ProteinQ9NSK0 (Uniprot-TrEMBL)
Kinesin-13 dimers R-HSA-990485 (Reactome)
Kinesin-3 dimers R-HSA-984608 (Reactome)
Kinesins:Dynactin:microtubuleComplexR-HSA-2213219 (Reactome)
LAG3 ProteinP18627 (Uniprot-TrEMBL)
LAG3:MHC IIComplexR-HSA-8856203 (Reactome)
LAG3ProteinP18627 (Uniprot-TrEMBL)
LGMNProteinQ99538 (Uniprot-TrEMBL)
MHC II alpha beta heterodimerComplexR-HSA-2213186 (Reactome)
MHC II:CLIPComplexR-HSA-2130574 (Reactome)
MHC II:lip10 nonamerComplexR-HSA-2130723 (Reactome)
MHC II:lip22 nonamerComplexR-HSA-2130680 (Reactome)
MHC class II alpha/beta dimerComplexR-HSA-2213189 (Reactome)
MHC class II

alpha/beta/Ii

nonamer
ComplexR-HSA-2130431 (Reactome)
MHC class II

alpha/beta/Ii

nonamer
ComplexR-HSA-2130467 (Reactome)
MHC class II epitopesR-ALL-2213226 (Reactome)
MHC class II epitopes R-ALL-2213226 (Reactome)
MHC class II epitopes R-ALL-2213228 (Reactome)
Microtubule protofilament R-HSA-8982424 (Reactome)
Nonameric complex in COPII vesicleComplexR-HSA-2213211 (Reactome)
Nonameric complexComplexR-HSA-2130477 (Reactome)
Nonameric complexComplexR-HSA-2130491 (Reactome)
Nonameric complexComplexR-HSA-2130531 (Reactome)
Nonameric complexComplexR-HSA-2130532 (Reactome)
Nonameric complexComplexR-HSA-2214394 (Reactome)
OSBPL1A ProteinQ9BXW6 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:18367 (ChEBI)
RAB7:RILP:ORP1L complexComplexR-HSA-2213215 (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)
TGN-lysosome vesicle

with nonameric

complex
ComplexR-HSA-2213234 (Reactome)
alpha beta dimer:Ii trimer:calnexinComplexR-HSA-2213212 (Reactome)
peptide free MHC II:HLA-DMComplexR-HSA-2213227 (Reactome)
peptide loaded MHC class IIComplexR-HSA-2213223 (Reactome)
peptide loaded MHC class IIComplexR-HSA-2213232 (Reactome)
unfolded antigenR-ALL-2213225 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
2xMHC II alpha beta

heterodimer:alpha beta dimer:Ii

trimer:calnexin
ArrowR-HSA-2213241 (Reactome)
2xMHC II alpha beta

heterodimer:alpha beta dimer:Ii

trimer:calnexin
R-HSA-8951500 (Reactome)
2xMHC II alpha beta

heterodimer:alpha beta dimer:Ii

trimer
ArrowR-HSA-8951500 (Reactome)
ADPArrowR-HSA-2213248 (Reactome)
AP-1 Complex:Arf1-GTP:Clathrin Triskelion:Nonameric complexArrowR-HSA-2130619 (Reactome)
AP-1 Complex:Arf1-GTP:Clathrin Triskelion:Nonameric complexR-HSA-8951498 (Reactome)
AP-1 Clathrin coated nonameric complexArrowR-HSA-8951498 (Reactome)
AP-1 Clathrin coated nonameric complexR-HSA-2130641 (Reactome)
AP-1 ComplexArrowR-HSA-2213236 (Reactome)
AP-1 ComplexR-HSA-2130619 (Reactome)
ARP-1ArrowR-HSA-2213248 (Reactome)
ARP-1R-HSA-2213248 (Reactome)
ATPR-HSA-2213248 (Reactome)
AntigenArrowR-HSA-2130627 (Reactome)
AntigenR-HSA-2130627 (Reactome)
AntigenR-HSA-2213240 (Reactome)
Arf1-GDPArrowR-HSA-8951498 (Reactome)
Arf1-GTPR-HSA-2130619 (Reactome)
CANXArrowR-HSA-8951500 (Reactome)
CANXR-HSA-2130478 (Reactome)
CD74(81-104)ArrowR-HSA-2213246 (Reactome)
COPIIArrowR-HSA-2213243 (Reactome)
COPIIR-HSA-2130731 (Reactome)
Cathepsinmim-catalysisR-HSA-2130349 (Reactome)
Cathepsinmim-catalysisR-HSA-2130504 (Reactome)
Cathepsinmim-catalysisR-HSA-2130706 (Reactome)
Clathrin TriskelionArrowR-HSA-2213236 (Reactome)
Clathrin TriskelionR-HSA-2130619 (Reactome)
Clathrin coated MHC

class II alpha/beta/Ii

nonamer
ArrowR-HSA-2130640 (Reactome)
Clathrin coated MHC

class II alpha/beta/Ii

nonamer
ArrowR-HSA-2130725 (Reactome)
Clathrin coated MHC

class II alpha/beta/Ii

nonamer
R-HSA-2130486 (Reactome)
Clathrin coated MHC

class II alpha/beta/Ii

nonamer
R-HSA-2130725 (Reactome)
Clathrin:AP-2 complexR-HSA-2130640 (Reactome)
Clathrin:AP2 complexArrowR-HSA-2130486 (Reactome)
Dynamin-1/2/3mim-catalysisR-HSA-2130725 (Reactome)
DynaminArrowR-HSA-2130641 (Reactome)
DynaminR-HSA-2130619 (Reactome)
Dynaminmim-catalysisR-HSA-2130641 (Reactome)
Dynein:Dynactin:microtubuleArrowR-HSA-2213248 (Reactome)
Dynein:Dynactin:microtubuleR-HSA-2213248 (Reactome)
GDPArrowR-HSA-2130641 (Reactome)
GDPArrowR-HSA-2130725 (Reactome)
GTPR-HSA-2130641 (Reactome)
GTPR-HSA-2130725 (Reactome)
H2OR-HSA-2130725 (Reactome)
HLA II alpha chainR-HSA-2213239 (Reactome)
HLA II beta chainR-HSA-2213239 (Reactome)
HLA-DM/HLA-DOArrowR-HSA-2213244 (Reactome)
HLA-DM/HLA-DOR-HSA-2213246 (Reactome)
IFI30mim-catalysisR-HSA-2213240 (Reactome)
Invariant chain trimerR-HSA-2130478 (Reactome)
Kinesins:Dynactin:microtubuleArrowR-HSA-2213248 (Reactome)
Kinesins:Dynactin:microtubuleR-HSA-2213248 (Reactome)
LAG3:MHC IIArrowR-HSA-8856157 (Reactome)
LAG3R-HSA-8856157 (Reactome)
LGMNmim-catalysisR-HSA-2130336 (Reactome)
MHC II alpha beta heterodimerArrowR-HSA-2213239 (Reactome)
MHC II alpha beta heterodimerR-HSA-2130478 (Reactome)
MHC II alpha beta heterodimerR-HSA-2213241 (Reactome)
MHC II:CLIPArrowR-HSA-2130349 (Reactome)
MHC II:CLIPR-HSA-2213246 (Reactome)
MHC II:lip10 nonamerArrowR-HSA-2130504 (Reactome)
MHC II:lip10 nonamerR-HSA-2130349 (Reactome)
MHC II:lip22 nonamerArrowR-HSA-2130336 (Reactome)
MHC II:lip22 nonamerR-HSA-2130504 (Reactome)
MHC class II alpha/beta dimerR-HSA-8856157 (Reactome)
MHC class II

alpha/beta/Ii

nonamer
ArrowR-HSA-2130378 (Reactome)
MHC class II

alpha/beta/Ii

nonamer
ArrowR-HSA-2130500 (Reactome)
MHC class II

alpha/beta/Ii

nonamer
R-HSA-2130500 (Reactome)
MHC class II

alpha/beta/Ii

nonamer
R-HSA-2130640 (Reactome)
MHC class II epitopesArrowR-HSA-2130706 (Reactome)
MHC class II epitopesR-HSA-2213244 (Reactome)
Nonameric complex in COPII vesicleArrowR-HSA-2130731 (Reactome)
Nonameric complex in COPII vesicleR-HSA-2213243 (Reactome)
Nonameric complexArrowR-HSA-2130393 (Reactome)
Nonameric complexArrowR-HSA-2130486 (Reactome)
Nonameric complexArrowR-HSA-2213235 (Reactome)
Nonameric complexArrowR-HSA-2213236 (Reactome)
Nonameric complexArrowR-HSA-2213243 (Reactome)
Nonameric complexR-HSA-2130336 (Reactome)
Nonameric complexR-HSA-2130378 (Reactome)
Nonameric complexR-HSA-2130393 (Reactome)
Nonameric complexR-HSA-2130619 (Reactome)
Nonameric complexR-HSA-2130731 (Reactome)
Nonameric complexR-HSA-2213235 (Reactome)
PiArrowR-HSA-2130641 (Reactome)
PiArrowR-HSA-2130725 (Reactome)
PiArrowR-HSA-8951498 (Reactome)
R-HSA-2130336 (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.
R-HSA-2130349 (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).
R-HSA-2130378 (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.
R-HSA-2130393 (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.
R-HSA-2130478 (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).
R-HSA-2130486 (Reactome) MHC II:Ii complexes bound to clathrin-coated vesicles rapidly fuse with endosomes.
R-HSA-2130500 (Reactome) On reaching the cell surface, transport carrier vesicles insert the cargo MHC II:Ii complex into the plasma membrane.
R-HSA-2130504 (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.
R-HSA-2130619 (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).
R-HSA-2130627 (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).
R-HSA-2130640 (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).
R-HSA-2130641 (Reactome) Budding vesicles loaded with the nonameric complex bud off from the TGN to reach the late-endosome/lysosome membrane.
R-HSA-2130706 (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.
R-HSA-2130725 (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).
R-HSA-2130731 (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).
R-HSA-2213235 (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).
R-HSA-2213236 (Reactome) On reaching the late endosomes/lysosomes the TGN-lysosome vesicle uncoats and fuses with the lysosome to releases the MHC II nonameric complex.
R-HSA-2213239 (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.
R-HSA-2213240 (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).
R-HSA-2213241 (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.
R-HSA-2213243 (Reactome) The COPII vesicle uncoats and fuses with the cis-Golgi, releasing the MHC II:Ii complex into the Golgi.
R-HSA-2213244 (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).
R-HSA-2213246 (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).
R-HSA-2213248 (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).
R-HSA-8856157 (Reactome) Melanomas often express MHC II molecules along with tumor-associated and tumor-specific Ags, which could make these tumors detectable and elemintaed by the immune system. However the expression of MHC II molecules by melanoma cells has been instead associated with poor prognosis (Ruiter et al. 1991, Deffrennes et al. 2001, Ostmeier et al. 2001, Martins et al. 2009). The exact role that MHC II might have in melanoma progression is unclear; it was suggested that MHC II can be involved in the escape of melanoma cells from immune surveillance. Lymphocyte-activation gene 3 (LAG3) belongs to Ig superfamily and is expressed by various subsets of tumor-infiltrating leukocytes. LAG3 is a natural ligand for MHC II and binds MHC II with a much higher avidity than CD4. LAG3 protects MHC II positive melanoma cells from apoptosis. Hemon et al proposes that LAG3-MHC II molecular interaction as a novel pathway enabling melanoma cells not only to escape immune attack but also to counter drug effects and to survive (Hemon et al. 2011).
R-HSA-8951498 (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).
R-HSA-8951500 (Reactome) Calnexin disassociates on egress of the nonameric complex from the ER.
RAB7:RILP:ORP1L complexArrowR-HSA-2213248 (Reactome)
RAB7:RILP:ORP1L complexR-HSA-2213248 (Reactome)
SH3GL2ArrowR-HSA-2130486 (Reactome)
SH3GL2R-HSA-2130725 (Reactome)
SPTBN2ArrowR-HSA-2213248 (Reactome)
SPTBN2R-HSA-2213248 (Reactome)
TGN-lysosome vesicle

with nonameric

complex
ArrowR-HSA-2130641 (Reactome)
TGN-lysosome vesicle

with nonameric

complex
R-HSA-2213236 (Reactome)
alpha beta dimer:Ii trimer:calnexinArrowR-HSA-2130478 (Reactome)
alpha beta dimer:Ii trimer:calnexinR-HSA-2213241 (Reactome)
peptide free MHC II:HLA-DMArrowR-HSA-2213246 (Reactome)
peptide free MHC II:HLA-DMR-HSA-2213244 (Reactome)
peptide loaded MHC class IIArrowR-HSA-2213244 (Reactome)
peptide loaded MHC class IIArrowR-HSA-2213248 (Reactome)
peptide loaded MHC class IIR-HSA-2213248 (Reactome)
unfolded antigenArrowR-HSA-2213240 (Reactome)
unfolded antigenR-HSA-2130706 (Reactome)
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