HLA class II histocompatibility antigen, DP alpha 1 chain (DP(W3)) (DP(W4)) (HLA-SB alpha chain) (MHC class II DP3-alpha) (MHC class II DPA1)
1_MRPED 6_ RMFHI 11_ RAVIL 16_ RALSL 21_ AFLLS 26_ LRGAG 31_ AIKAD 36_ HVSTY 41_ AAFVQ 46_ THRPT 51_ GEFMF 56_ EFDED 61_ EMFYV 66_ DLDKK 71_ ETVWH 76_ LEEFG 81_ QAFSF 86_ EAQGG 91_ LANIA 96_ ILNNN 101_ LNTLI 106_ QRSNH 111_ TQATN 116_ DPPEV 121_ TVFPK 126_ EPVEL 131_ GQPNT 136_ LICHI 141_ DKFFP 146_ PVLNV 151_ TWLCN 156_ GELVT 161_ EGVAE 166_ SLFLP 171_ RTDYS 176_ FHKFH 181_ YLTFV 186_ PSAED 191_ FYDCR 196_ VEHWG 201_ LDQPL 206_ LKHWE 211_ AQEPI 216_ QMPET 221_ TETVL 226_ CALGL 231_ VLGLV 236_ GIIVG 241_ TVLII 246_ KSLRS 251_GHDPR
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