HLA-DRA
HLA-DRA is one of the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha and a beta chain, both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5. [provided by RefSeq, Jul 2008]
Function
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).
Biological Process
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
Cellular Location
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).
Topology
Extracellular: 26-216
Helical: 217-239
Cytoplasmic: 240-254
PTM
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.
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Datasheet