HLA class II histocompatibility antigen, DQ beta 1 chain (MHC class II antigen DQB1)
1_MSWKK 6_ ALRIP 11_ GGLRA 16_ ATVTL 21_ MLAML 26_ STPVA 31_ EGRDS 36_ PEDFV 41_ YQFKA 46_ MCYFT 51_ NGTER 56_ VRYVT 61_ RYIYN 66_ REEYA 71_ RFDSD 76_ VEVYR 81_ AVTPL 86_ GPPDA 91_ EYWNS 96_ QKEVL 101_ ERTRA 106_ ELDTV 111_ CRHNY 116_ QLELR 121_ TTLQR 126_ RVEPT 131_ VTISP 136_ SRTEA 141_ LNHHN 146_ LLVCS 151_ VTDFY 156_ PAQIK 161_ VRWFR 166_ NDQEE 171_ TTGVV 176_ STPLI 181_ RNGDW 186_ TFQIL 191_ VMLEM 196_ TPQHG 201_ DVYTC 206_ HVEHP 211_ SLQNP 216_ ITVEW 221_ RAQSE 226_ SAQSK 231_ MLSGI 236_ GGFVL 241_ GLIFL 246_ GLGLI 251_ IHHRS 256_QKGLL
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