HLA E

Major histocompatibility complex, class I, E, also known as HLA-E, is a human gene.

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.