HLA class II histocompatibility antigen, DP beta 1 chain (HLA class II histocompatibility antigen, DP(W4) beta chain) (MHC class II antigen DPB1)
1_MMVLQ 6_ VSAAP 11_ RTVAL 16_ TALLM 21_ VLLTS 26_ VVQGR 31_ ATPEN 36_ YLFQG 41_ RQECY 46_ AFNGT 51_ QRFLE 56_ RYIYN 61_ REEFA 66_ RFDSD 71_ VGEFR 76_ AVTEL 81_ GRPAA 86_ EYWNS 91_ QKDIL 96_ EEKRA 101_ VPDRM 106_ CRHNY 111_ ELGGP 116_ MTLQR 121_ RVQPR 126_ VNVSP 131_ SKKGP 136_ LQHHN 141_ LLVCH 146_ VTDFY 151_ PGSIQ 156_ VRWFL 161_ NGQEE 166_ TAGVV 171_ STNLI 176_ RNGDW 181_ TFQIL 186_ VMLEM 191_ TPQQG 196_ DVYTC 201_ QVEHT 206_ SLDSP 211_ VTVEW 216_ KAQSD 221_ SARSK 226_ TLTGA 231_ GGFVL 236_ GLIIC 241_ GVGIF 246_ MHRRS 251_KKVQR
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