Skip to main content

HLA-DRA

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
  • HLA-DRA1
  • MHC class II antigen DRA

Target type

Proteins

Primary research area

Immuno-oncology

Other research areas

  • Immunology & Infectious Disease

Molecular weight

28621Da

We found 53 products in 5 categories

Assay Kits

Target

Reactive species

Detection method

Proteins & Peptides

Target

Species of origin

Nature

Multiplex Kits

Cell Lines & Lysates

Target

Cell type

Species or organism