HLA-C
Description
The HLA-C (major histocompatibility complex, class I, C) is a protein-coding gene located on chromosome 6.
HLA-C (Human Leukocyte Antigen-C) belongs to the MHC class I heavy chain receptors. The C receptor is a heterodimer consisting of a HLA-C mature gene product and β2-microglobulin. The mature C chain is anchored in the membrane. MHC Class I molecules, like HLA-C, are expressed in nearly all cells, and present small peptides to the immune system which surveys for non-self peptides. HLA-C is a locus on chromosome 6, which encodes for many HLA-C alleles that are Class-I MHC receptors. HLA-C, localized proximal to the HLA-B locus, is located on the distal end of the HLA region. Most HLA-C:B haplotypes are in strong linkage disequilibrium and many are as ancient as the human species itself.
HLA-C is an antigen-presenting major histocompatibility complex class I (MHCI) molecule that plays a critical role in both reproduction and antiviral immunity. In conjunction with beta-2 microglobulin (B2M), HLA-C presents a restricted range of self and viral peptides to the immune system, serving as a primary ligand for both inhibitory and activating killer immunoglobulin receptors (KIRs) expressed on natural killer (NK) cells. During pregnancy, HLA-C mediates the interaction of extravillous trophoblasts with KIRs on uterine NK cells, thereby regulating trophoblast invasion, which is crucial for placentation and overall fetal growth. In the context of viral infection, HLA-C may present viral peptides with low affinity for KIRs, effectively impeding KIR-mediated inhibition through peptide antagonism and promoting lysis of infected cells. Furthermore, HLA-C presents a limited repertoire of viral peptides on antigen-presenting cells for recognition by alpha-beta T cell receptors (TCRs) on HLA-C-restricted CD8-positive T cells. This interaction guides antigen-specific T cell immune responses, eliminating infected cells, particularly in chronic viral infection settings such as HIV-1 or CMV infection. The recognition of peptide-MHC complexes by TCRs is a two-part process: the peptide is responsible for the fine specificity of antigen recognition, while MHC residues determine the MHC restriction of T cells. HLA-C typically presents intracellular peptide antigens of 9 amino acids, derived from cytosolic proteolysis via the proteasome. HLA-C can bind various peptides containing allele-specific binding motifs, primarily defined by anchor residues at positions 2 and 9. HLA-C exhibits a preference for peptides with a restricted range of hydrophobic or aromatic amino acids (Phe, Ile, Leu, Met, Val, and Tyr) at the C-terminal anchor.
HLA-C is also known as D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1.
