HLA-A
HLA-A is a class I major histocompatibility complex molecule: the cell-surface display protein that presents intracellular peptide fragments to CD8 T cells, making the interior of every cell visible to immune surveillance.
Function
HLA-A binds short peptides (8-10 amino acids) generated by the proteasome from the cell’s own proteins - including proteins from viruses and from mutated oncogenes - and carries them to the cell surface for inspection by CD8 T cells. A T cell whose receptor recognizes a presented peptide as foreign kills the displaying cell. Each person expresses three HLA-A alleles (one from each parent, out of thousands in the population), and the allele set determines which peptides an individual can present, which is the molecular basis of tissue-transplant matching and of individual variation in antiviral and antitumor immunity.
In cancer
Tumor cells reduce HLA-A display - through loss of heterozygosity, down-regulation of the processing machinery, or viral interference - because a cell presenting tumor-antigen peptides is a target for cytotoxic T cells. Reduced HLA class I expression is one of the standard escape phenotypes of immunoediting, and it explains why tumors with low HLA respond poorly to checkpoint inhibitors: the brake can be released only if the tumor still displays its antigens.
Notes
- Human gene symbol: HLA-A; UniProt P04439 (HLA-A*01:01); 365 amino acids; MHC class I heavy chain, pairs with β2-microglobulin.
- The HLA-A locus is the most polymorphic coding locus in the human genome.