Recombinant Human HLA class II histocompatibility antigen, DR alpha chain (HLA-DRA)

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)

Subcellular Location

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)

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)

Subunit

(Microbial infection) Interacts with Staphylococcus aureus enterotoxin A/entA, enterotoxin B/entB, enterotoxin C1/entC1, enterotoxin D/entD, and enterotoxin H/entH

• Lee J.S. et al. Sequence of an HLA-DR alpha-chain cDNA clone and intron-exon organization of the corresponding gene. — Nature (1982)
• Kajimura Y. et al. Cloning the heavy chain of human HLA-DR antigen using synthetic oligodeoxyribonucleotides as hybridization probes. — DNA (1983)
• Koppelman B. et al. Rapid nonlysosomal degradation of assembled HLA class II glycoproteins incorporating a mutant DR alpha-chain. — J. Immunol. (1990)
• Schamboeck A. et al. Organization of the transcriptional unit of a human class II histocompatibility antigen: HLA-DR heavy chain. — Nucleic Acids Res. (1983)
• Das H.K. et al. Structure and nucleotide sequence of the heavy chain gene of HLA-DR. — Proc. Natl. Acad. Sci. U.S.A. (1983)
• Das H.K. et al. PubMed: CI-D7IQH4GN83NP7 — Proc. Natl. Acad. Sci. U.S.A. (1983)
• Ebert L. et al. Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201). (JUN-)
• Mungall A.J. et al. The DNA sequence and analysis of human chromosome 6. — Nature (2003)