Abstract
HLA-E is a nonclassical member of the major histocompatibility complex class I gene locus. HLA-E protein shares a high level of homology with MHC Ia classical proteins: it has similar tertiary structure, associates with β2-microglobulin, and is able to present peptides to cytotoxic lymphocytes. The main function of HLA-E under normal conditions is to present peptides derived from the leader sequences of classical HLA class I proteins, thus serving for monitoring of expression of these molecules performed by cytotoxic lymphocytes. However, opposite to multiallelic classical MHC I genes, HLA-E in fact has only two alleles-HLA-E*01:01 and HLA-E*01:03-which differ by one nonsynonymous amino acid substitution at position 107, resulting in an arginine in HLA-E*01:01 (HLA-E(R)) and glycine in HLA-E*01:03 (HLA-E(G)). In contrast to HLA-E(R), HLA-E(G) has higher affinity to peptide, higher surface expression, and higher thermal stability of the corresponding protein, and it is more ancient than HLA-E(R), though both alleles are presented in human populations in nearly equal frequencies. In the current review, we aimed to uncover the reason of the expansion of the younger allele, HLA-E(R), by analysis of associations of both HLA-E alleles with a number of diseases, including viral and bacterial infections, cancer, and autoimmune disorders.