HLA-DRA
Description
The HLA-DRA (major histocompatibility complex, class II, DR alpha) is a protein-coding gene located on chromosome 6.
HLA-DRA encodes the alpha subunit of HLA-DR, a protein involved in the immune system. Unlike other MHC class II alpha chains, HLA-DRA is practically invariable. However, it can pair with beta chains from three different DR beta loci, DRB1, DRB3, DRB4, and DRB5, resulting in four potential HLA-DR isoforms in an individual. The protein is a heterodimer consisting of an alpha (DRα) and a beta chain (DRβ), 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.
HLA-DRA, also known as MHC class II antigen DRA, is an alpha chain of the major histocompatibility complex class II (MHCII) molecule. It forms a complex with the beta chain HLA-DRB, presenting antigenic peptides to professional antigen-presenting cells (APCs) for recognition by alpha-beta T cell receptors (TCRs) on HLA-DR-restricted CD4-positive T cells. This interaction guides antigen-specific T-helper effector functions, including antibody-mediated immune response and macrophage activation, ultimately leading to the elimination of infectious agents and transformed cells. HLA-DRA typically presents extracellular peptide antigens of 10 to 30 amino acids that are derived from the proteolysis of endocytosed antigens in lysosomes. It also presents antigenic peptides in the tumor microenvironment, likely generated via phagocytosis of apoptotic tumor cells or macropinocytosis of secreted tumor proteins. Furthermore, it presents peptides from intracellular proteins trapped in autolysosomes after macroautophagy, a crucial process for T cell selection in the thymus and central immune tolerance. The selection of immunodominant epitopes follows two processing modes: 'bind first, cut/trim later' for pathogen-derived antigens and 'cut first, bind later' for autoantigens/self-peptides. 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.
HLA-DRA is also known as HLA-DRA1.
