|Major histocompatibility complex, class I, E|
PDB rendering based on 1kpr.
|Symbols||; DKFZp686P19218; EA1.2; EA2.1; HLA-6.2; MHC|
|External IDs||Template:OMIM5 Template:MGI|
|RNA expression pattern|
|Template:GNF Ortholog box|
Major histocompatibility complex, class I, E, also known as HLA-E, is a human gene.
HLA-E belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-E binds a restricted subset of peptides derived from the leader peptides of other class I molecules. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail.
HLA-E is a protein that is a member of the HLA family. It is one of a family of molecules known as MHC class Ib and has a very specialized role in cell recognition by NK cells (Natural Killer). HLA-E is very highly conserved and presents a small repertoire of peptides of various origins. HLA-E is expressed ubiquitously. The primary peptides HLA-E binds are derived from the leader sequence of other HLA class Ia molecules, such as HLA-A, B, C, G.These proteins bind to the Peptide binding groove of the HLA-E molecule, and this allows it to be expressed on on the surface. NK cells recognise bound HLA-E+Peptide combination using the heterodimeric inhibitory receptor CD94/NKG2A or the activating receptor NKG2C/CD94 . When CD94/NKG2A is stimulated, it produces an inhibitory effect on the cytotoxic activity of the NK cell to prevent cell lysis.
A number of viruses have evolved to express proteins that inhibit the expression of MHC I molecules on cell surface of cells they infect, thereby preventing Antigen presentation that would allow the Immune system to recognise infection. NK cells therefore identify cells that are exhibiting such characteristics of viral infection.
HLA E is also reported to interact with the T-cell receptor. HLA-E presents a peptide (VMAPRTLIL) derived from the UL40 protein from cytomegalovirus. This peptide is highly similar to the leader peptides derived from other HLA molecules and acts as a surrogate "leader peptide" and interacts with CD94/NKG2 receptors. This engagement relays into an overall inhibitory effect on NK-cell meditated cytotoxicity.
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