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 miroenvironment has been implicated in the regulation of antigen loading into MHC II molecules; increased acidification produces increased proteolysis and efficient peptide loading. Genetic variation in HLA-DRB1 is a cause of susceptibility to sarcoidosis type 1 (SS1). Sarcoidosis is an idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved. Belongs to the MHC class II family. Note: This description may include information from UniProtKB.
Protein type: Membrane protein, integral
Cellular Component: Golgi membrane; membrane; lysosomal membrane; integral to plasma membrane; late endosome membrane; plasma membrane; trans-Golgi network membrane; MHC class II protein complex; external side of plasma membrane
Molecular Function: MHC class II receptor activity; peptide antigen binding
Biological Process: T-helper 1 type immune response; detection of bacterium; cytokine and chemokine mediated signaling pathway; antigen processing and presentation of exogenous peptide antigen via MHC class II; immunoglobulin production during immune response; T cell receptor signaling pathway; humoral immune response mediated by circulating immunoglobulin; negative regulation of T cell proliferation; inflammatory response to antigenic stimulus; regulation of interleukin-4 production; negative regulation of interferon-gamma production; T cell costimulation; immune response; protein tetramerization
Alt. Names/Synonyms: 2B11; cell surface glycoprotein; clone P2-beta-3; Clone P2-beta-4; DR-1; DR-16; DR-5; DR-8; DR1; DR16; DR5; DR8; DRB1; DRw10; DRw11; DRw8; FLJ75017; FLJ76359; HLA class II antigen beta chain; HLA class II histocompatibility antigen, DR-1 beta chain; HLA class II histocompatibility antigen, DRB1-1 beta chain; HLA class II histocompatibility antigen, DRB1-10 beta chain; HLA class II histocompatibility antigen, DRB1-11 beta chain; HLA class II histocompatibility antigen, DRB1-16 beta chain; HLA class II histocompatibility antigen, DRB1-3 chain; HLA class II histocompatibility antigen, DRB1-8 beta chain; HLA-DR-beta 1; HLA-DR1B; HLA-DRB; HLA-DRB1; HLA-DRB1*; human leucocyte antigen DRB1; leucocyte antigen DR beta 1 chain; leucocyte antigen DRB1; lymphocyte antigen DRB1; major histocompatibility complex, class II, DR beta 1; MHC class I antigen DRB1*1; MHC class I antigen DRB1*16; MHC class I antigen DRB1*8; MHC class II antigen DRB1*1; MHC class II antigen DRB1*10; MHC class II antigen DRB1*11; MHC class II antigen DRB1*3; MHC class II antigen HLA-DR13; MHC class II HLA-DR beta 1 chain; MHC class II HLA-DR-beta cell surface glycoprotein; MHC class II HLA-DRw10-beta; SS1
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.