TARGETID

T83611

FORMERID

TTDS00471

UNIPROID

2B11_HUMAN

TARGNAME

MHC class II antigen DRB1*1 (HLA-DRB1)

GENENAME

HLA-DRB1

TARGTYPE

Successful target

SYNONYMS

HLA class II histocompatibility antigen, DRB1-1 beta chain; DR1; DR-1

FUNCTION

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.

PDBSTRUC

6CQR; 6CQJ; 4X5X; 4X5W; 4OV5

BIOCLASS

MHC class II

SEQUENCE

MVCLKLPGGSCMTALTVTLMVLSSPLALSGDTRPRFLWQPKRECHFFNGTERVRFLDRYFYNQEESVRFDSDVGEFRAVTELGRPDAEYWNSQKDILEQARAAVDTYCRHNYGVVESFTVQRRVQPKVTVYPSKTQPLQHHNLLVCSVSGFYPGSIEVRWFLNGQEEKAGMVSTGLIQNGDWTFQTLVMLETVPRSGEVYTCQVEHPSVTSPLTVEWRARSESAQSKMLSGVGGFVLGLLFLGAGLFIYFRNQKGHSGLQPTGFLS

DRUGINFO

Glatiramer Acetate

WIKIPATH

WP1799:Costimulation by the CD28 family

WIKIPATH

WP1836:Interferon gamma signaling

WIKIPATH

WP1927:TCR signaling

WIKIPATH

WP2679:MHC class II antigen presentation

REACPATH

R-HSA-202427:Phosphorylation of CD3 and TCR zeta chains

REACPATH

R-HSA-202430:Translocation of ZAP-70 to Immunological synapse

REACPATH

R-HSA-202433:Generation of second messenger molecules

REACPATH

R-HSA-2132295:MHC class II antigen presentation