HLA class II histocompatibility antigen, DR beta 5 chain (DR beta-5) (DR2-beta-2) (Dw2) (MHC class II antigen DRB5)
1_MVCLK 6_ LPGGS 11_ YMAKL 16_ TVTLM 21_ VLSSP 26_ LALAG 31_ DTRPR 36_ FLQQD 41_ KYECH 46_ FFNGT 51_ ERVRF 56_ LHRDI 61_ YNQEE 66_ DLRFD 71_ SDVGE 76_ YRAVT 81_ ELGRP 86_ DAEYW 91_ NSQKD 96_ FLEDR 101_ RAAVD 106_ TYCRH 111_ NYGVG 116_ ESFTV 121_ QRRVE 126_ PKVTV 131_ YPART 136_ QTLQH 141_ HNLLV 146_ CSVNG 151_ FYPGS 156_ IEVRW 161_ FRNSQ 166_ EEKAG 171_ VVSTG 176_ LIQNG 181_ DWTFQ 186_ TLVML 191_ ETVPR 196_ SGEVY 201_ TCQVE 206_ HPSVT 211_ SPLTV 216_ EWRAQ 221_ SESAQ 226_ SKMLS 231_ GVGGF 236_ VLGLL 241_ FLGAG 246_ LFIYF 251_ KNQKG 256_ HSGLH 261_PTGLV
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