HLA class II histocompatibility antigen, DQ beta 2 chain (HLA class II histocompatibility antigen, DX beta chain) (MHC class II antigen DQB2)
1_MSWKM 6_ ALQIP 11_ GGFWA 16_ AAVTV 21_ MLVML 26_ STPVA 31_ EARDF 36_ PKDFL 41_ VQFKG 46_ MCYFT 51_ NGTER 56_ VRGVA 61_ RYIYN 66_ REEYG 71_ RFDSD 76_ VGEFQ 81_ AVTEL 86_ GRSIE 91_ DWNNY 96_ KDFLE 101_ QERAA 106_ VDKVC 111_ RHNYE 116_ AELRT 121_ TLQRQ 126_ VEPTV 131_ TISPS 136_ RTEAL 141_ NHHNL 146_ LVCSV 151_ TDFYP 156_ AQIKV 161_ RWFRN 166_ DQEET 171_ AGVVS 176_ TSLIR 181_ NGDWT 186_ FQILV 191_ MLEIT 196_ PQRGD 201_ IYTCQ 206_ VEHPS 211_ LQSPI 216_ TVEWR 221_ AQSES 226_ AQSKM 231_ LSGIG 236_ GFVLG 241_ LIFLG 246_ LGLII 251_ RHRGQ 256_ KGPRG 261_PPPAG
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