HLA-DRA
GeneName
HLA-DRA
Summary
HLA-DRA, also known as HLA DR or HLA DRA1, is a 29 kDa protein that is a component of the major histocompatibility complex (MHC) class II. It is primarily expressed on the surface of antigen-presenting cells, including dendritic cells, macrophages, and B cells. HLA-DRA plays a crucial role in the adaptive immune response by binding peptide antigens and presenting them to CD4+ T cells, facilitating T cell activation and differentiation. It is involved in various cellular compartments, including the plasma membrane, endosomes, and lysosomes, and is essential for the processing and presentation of both endogenous and exogenous antigens. The protein is also associated with the immunological synapse, where it interacts with T cell receptors to mediate immune responses.
Importance
HLA-DRA is relevant to: - Adaptive immunity and the activation of CD4+ T cells, which are vital for orchestrating immune responses - Autoimmune diseases, as its expression can influence the presentation of self-antigens and the development of tolerance - Vaccine development, particularly in designing effective immunogens that can elicit strong T cell responses - Transplantation biology, where its compatibility can affect graft acceptance and rejection
Top Products
For researchers investigating HLA-DRA, we highly recommend the top-selling recombinant antibody, Anti-HLA-DR antibody [TAL 1B5] (ab20181). This well-cited antibody has garnered 65 citations, reflecting its reliability and trust within the scientific community. It is validated for a variety of applications, including flow cytometry (FC), immunohistochemistry (IHC), western blotting (WB), and immunocytochemistry (ICC), making it an excellent choice for diverse experimental needs. The recombinant nature of this antibody ensures batch-to-batch consistency, providing researchers with confidence in their results. The Anti-HLA Class II DR4 antibody ELISA Kit (ab98106) is an excellent option for researchers looking to measure HLA-DRA levels in their samples.
Abcam Product Citation Summary
The data indicates that HLA-DRA is being studied in the context of cancer, particularly breast cancer and pancreatic ductal adenocarcinoma (PDA). The use of antibodies in both Western blotting and immunohistochemistry suggests a focus on understanding the expression and regulation of HLA-DRA in relation to immune responses and clinical outcomes.
Abcam Product Citation Table
Domain
The alpha-1 domain is a structural part of the peptide-binding cleft. It contains one alpha helix and 4 beta sheets, respectively forming part of the wall and the floor of the peptide-binding cleft. The other 4 beta sheets of the floor and the second alpha helix wall is formed by the beta-1 domain of HLA-DRB. Forms hydrogen bonds with the peptide main chain via conserved amino acids (PubMed:17583734, PubMed:29884618, PubMed:8145819, PubMed:9354468, PubMed:9782128). The peptide-bound alpha-1 domain forms hydrogen bonds with CDR2 and CDR3 alpha-domain of TCR (PubMed:29884618).
The alpha-2 Ig-like domain mediates the interaction with CD4 coreceptor.
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:15265931, PubMed:15322540, PubMed:17334368, PubMed:22327072, PubMed:24190431, PubMed:27591323, PubMed:29884618, PubMed:31495665, PubMed:8145819, PubMed:9075930). 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).
Post-translational modifications
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.
Sequence Similarities
Belongs to the MHC class II family.
Tissue Specificity
Expressed in professional APCs: macrophages, dendritic cells and B cells (at protein level) (PubMed:15322540, PubMed:23783831, PubMed:31495665). Expressed in thymic epithelial cells (at protein level) (PubMed:23783831).
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Endoplasmic reticulum membrane
- Single-pass type I membrane protein
- Early endosome membrane
- Single-pass type I membrane protein
- Late endosome membrane
- Single-pass type I membrane protein
- Lysosome membrane
- Single-pass type I membrane protein
- Autolysosome membrane
- Single-pass type I membrane protein
- The MHCII complex transits through a number of intracellular compartments in the endocytic pathway until it reaches the cell membrane for antigen presentation (PubMed:18305173, PubMed:9075930). Component of immunological synapses at the interface between T cell and APC (PubMed:15322540, PubMed:29884618).
Alternative names
HLA-DRA1, HLA-DRA, MHC class II antigen DRA
Database links
swissprot:P01903 entrezGene:3123 entrezGene:3115 entrezGene:3125 entrezGene:3126 entrezGene:3127 swissprot:P13763 entrezGene:972 swissprot:P04440 entrezGene:3122 swissprot:P01916 swissprot:Q30118 swissprot:P04232 omim:142858 omim:142860 omim:604776
Other research areas
- Immunology & Infectious Disease