HLA DRA

Major histocompatibility complex (MHC) class II molecules destined for presentation to CD4+ helper T-cells is determined by two key events. These events include the dissociation of class II-associated invariant chain peptides (CLIP) from an antigen binding groove in mhc ii-a/b dimers through the activity of MHC molecules HLA-DM and -DO, and subsequent peptide antigen binding. Accumulating in endosomal/lysosomal compartments and on the surface of B cells, HLA-DM, -DO molecules regulate the dissociation of CLIP and the subsequent binding of exogenous peptides to HLA class II molecules (HLA-DR, DQ, DP and DR) by sustaining a conformation that favors peptide exchange.

Leukocyte Antigen DR, Alpha Subunit

An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the beta chain HLA-DRB, displays antigenic peptides on professional antigen presenting cells (APCs) for recognition by alpha-beta T cell receptor (TCR) on HLA-DR-restricted CD4-positive T cells. This guides antigen-specific T-helper effector functions, both antibody-mediated immune response and macrophage activation, to ultimately eliminate the infectious agents and transformed cells (PubMed:29884618, PubMed:17334368, PubMed:8145819, PubMed:15322540, PubMed:22327072, PubMed:27591323, PubMed:31495665, PubMed:15265931, PubMed:9075930, PubMed:24190431).

Typically presents extracellular peptide antigens of 10 to 30 amino acids that arise from proteolysis of endocytosed antigens in lysosomes (PubMed:8145819).

In the tumor microenvironment, presents antigenic peptides that are primarily generated in tumor-resident APCs likely via phagocytosis of apoptotic tumor cells or macropinocytosis of secreted tumor proteins (PubMed:31495665).

Presents peptides derived from intracellular proteins that are trapped in autolysosomes after macroautophagy, a mechanism especially relevant for T cell selection in the thymus and central immune tolerance (PubMed:17182262, PubMed:23783831).

The selection of the immunodominant epitopes follows two processing modes: 'bind first, cut/trim later' for pathogen-derived antigenic peptides and 'cut first, bind later' for autoantigens/self-peptides (PubMed:25413013).

The anchor residue at position 1 of the peptide N-terminus, usually a large hydrophobic residue, is essential for high affinity interaction with MHCII molecules (PubMed:8145819).

Adaptive immune response Source: UniProtKB-KW
Antigen processing and presentation of endogenous peptide antigen via MHC class II Source: UniProtKB
Antigen processing and presentation of exogenous peptide antigen via MHC class II Source: UniProtKB
Antigen processing and presentation of peptide or polysaccharide antigen via MHC class II Source: UniProtKB
Cognition Source: UniProtKB
Immune response Source: UniProtKB
Myeloid dendritic cell antigen processing and presentation Source: UniProtKB
Peptide antigen assembly with MHC class II protein complex Source: UniProtKB
Positive regulation of CD4-positive, alpha-beta T cell activation Source: UniProtKB
Positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation Source: UniProtKB
Positive regulation of memory T cell differentiation Source: UniProtKB
Positive regulation of T cell activation Source: GO_Central
Positive regulation of T cell mediated cytotoxicity Source: UniProtKB
Regulation of T-helper cell differentiation Source: UniProtKB

Early endosome membrane; Late endosome membrane; Cell membrane; Endoplasmic reticulum membrane; Lysosome membrane; Autolysosome membrane. The MHCII complex transits through a number of intracellular compartments in the endocytic pathway until it reaches the cell membrane for antigen presentation (PubMed:9075930, PubMed:18305173). Component of immunological synapses at the interface between T cell and APC (PubMed:15322540, PubMed:29884618).

Extracellular: 26-216
Helical: 217-239
Cytoplasmic: 240-254

Ubiquitinated by MARCHF1 or MARCHF8 at Lys-244 leading to down-regulation of MHCII. When associated with ubiquitination of the beta chain at 'Lys-254', the down-regulation of MHCII may be highly effective.