Protein: HLA class II histocompatibility antigen, DR alpha chain (MHC class II antigen DRA) (P01903)
Organism: Homo sapiens (Human)
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. Typically presents extracellular peptide antigens of 10 to 30 amino acids that arise from proteolysis of endocytosed antigens in lysosomes. 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. 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. 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. 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.
Subcellular location: Cell membrane {ECO:0000269|PubMed:15322540, ECO:0000269|PubMed:18305173, ECO:0000269|PubMed:29884618}; Single-pass type I membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:18305173}; Single-pass type I membrane protein {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:19117940}; Single-pass type I membrane protein {ECO:0000255}. Late endosome membrane {ECO:0000269|PubMed:18305173, ECO:0000269|PubMed:19117940, ECO:0000269|PubMed:9075930}; Single-pass type I membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:18305173, ECO:0000269|PubMed:9075930}; Single-pass type I membrane protein {ECO:0000255}. Autolysosome membrane {ECO:0000269|PubMed:17182262}; Single-pass type I membrane protein. Note=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). {ECO:0000269|PubMed:15322540, ECO:0000269|PubMed:18305173, ECO:0000269|PubMed:29884618, ECO:0000269|PubMed:9075930}.
Interaction partners:
- HLA class II histocompatibility antigen gamma chain
- HLA class II histocompatibility antigen, DRB1 beta chain
- HLA class II histocompatibility antigen, DM alpha chain
- HLA class II histocompatibility antigen, DP alpha 1 chain
- HLA class II histocompatibility antigen, DR beta 5 chain
- HLA class II histocompatibility antigen, DM beta chain
- T-cell surface glycoprotein CD4
- HLA class II histocompatibility antigen, DP beta 1 chain beta chain)
- HLA class II histocompatibility antigen, DO beta chain
- HLA class II histocompatibility antigen, DQ beta 1 chain
Sequence:
MAISGVPVLGFFIIAVLMSAQESWAIKEEHVIIQAEFYLNPDQSGEFMFDFDGDEIFHVDMAKKETVWRLEEFGRFASFEAQGALANIAVDKANLEIMTKRSNYTPITNVPPEVTVLTNSPVELREPNVLICFIDKFTPPVVNVTWLRNGKPVTTGVSETVFLPREDHLFRKFHYLPFLPSTEDVYDCRVEHWGLDEPLLKHWEFDAPSPLPETTENVVCALGLTVGLVGIIIGTIFIIKGLRKSNAAERRGPL