HLA class II histocompatibility antigen, DQ alpha 2 chain (DX alpha chain) (HLA class II histocompatibility antigen, DQ(6) alpha chain) (HLA-DQA1) (MHC class II DQA2)
1_MILNK 6_ ALLLG 11_ ALALT 16_ AVMSP 21_ CGGED 26_ IVADH 31_ VASYG 36_ VNFYQ 41_ SHGPS 46_ GQYTH 51_ EFDGD 56_ EEFYV 61_ DLETK 66_ ETVWQ 71_ LPMFS 76_ KFISF 81_ DPQSA 86_ LRNMA 91_ VGKHT 96_ LEFMM 101_ RQSNS 106_ TAATN 111_ EVPEV 116_ TVFSK 121_ FPVTL 126_ GQPNT 131_ LICLV 136_ DNIFP 141_ PVVNI 146_ TWLSN 151_ GHSVT 156_ EGVSE 161_ TSFLS 166_ KSDHS 171_ FFKIS 176_ YLTFL 181_ PSADE 186_ IYDCK 191_ VEHWG 196_ LDEPL 201_ LKHWE 206_ PEIPA 211_ PMSEL 216_ TETLV 221_ CALGL 226_ SVGLM 231_ GIVVG 236_ TVFII 241_ QGLRS 246_VGASR
1: Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading