HLA-F

HLA class I histocompatibility antigen, alpha chain F is a protein that in humans is encoded by the HLA-F gene.

Function

HLA-F belongs to the non-classical HLA class I heavy chain paralogues. Compared to classical HLA I molecules it exhibits very few polymorphisms. This class I molecule mainly exists as a heterodimer associated with the invariant light chain beta-2 microglobulin. The heavy chain is approximately 42 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, the putative peptide binding sites, exon 4 encodes the alpha3 domain, exon 5 and 6 encode the transmembrane region and exons 7 and 8 the cytoplasmic tail. However, exons 7 and 8 (the cytoplasmic tail) are not translated due to an in-frame translation termination codon in exon 6.

HLA-F is currently the most enigmatic of the HLA molecules. Hence, its precise functions still remain to be resolved. Though, in contrast to other HLA molecules, it mainly resides intracellularly and rarely reaches the cell surface, e.g. upon activation of NK, B and T cells. Unlike classical HLA class I molecules, which possess ten highly conserved amino acids responsible for antigen recognition, HLA-F only has 5, suggesting a biological function different from peptide presentation. Data suggest that upon immune cell activation HLA-F binds free forms of HLA I and reaches the cell surface as heterodimer. In this way HLA-F stabilizes HLA I molecules that haven´t yet bound peptides, thereby acting as a chaperone and transporting the free HLA I to, on, and from the cell surface.