Dimorphism of HLA-E and Its Disease Association

• Main Authors: Leonid Kanevskiy, Sofya Erokhina, Polina Kobyzeva, Maria Streltsova, Alexander Sapozhnikov, Elena Kovalenko
• Format: Article
• Language: English
• Published: MDPI AG 2019-11-01
• Series: International Journal of Molecular Sciences
• Subjects: hla-e; peptide repertoire; antigen presentation; nk cells; nkg2 receptors
• Online Access: https://www.mdpi.com/1422-0067/20/21/5496

<i>HLA-E</i> 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 &#946;2-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 <i>MHC I</i> genes, <i>HLA-E</i> in fact has only two alleles&#8212;<i>HLA-E*01:01</i> and <i>HLA-E*01:03</i>&#8212;which differ by one nonsynonymous amino acid substitution at position 107, resulting in an arginine in <i>HLA-E*01:01</i> (<i>HLA-E^R</i>) and glycine in <i>HLA-E*01:03</i> (<i>HLA-E^G</i>). In contrast to <i>HLA-E^R,</i> <i>HLA-E^G</i> has higher affinity to peptide, higher surface expression, and higher thermal stability of the corresponding protein, and it is more ancient than <i>HLA-E^R</i>, 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, <i>HLA-E^R</i>, by analysis of associations of both <i>HLA-E</i> alleles with a number of diseases, including viral and bacterial infections, cancer, and autoimmune disorders.