HLA-E
Template:Short description Template:Cs1 config Template:Infobox gene HLA class I histocompatibility antigen, alpha chain E (HLA-E) also known as MHC class I antigen E is a protein that in humans is encoded by the HLA-E gene.[1] The human HLA-E is a non-classical MHC class I molecule that is characterized by a limited polymorphism and a lower cell surface expression than its classical paralogues. The functional homolog in mice is called Qa-1b, officially known as H2-T23.
Structure
Like other MHC class I molecules, HLA-E is a heterodimer consisting of an α heavy chain and a light chain (β-2 microglobulin). The heavy chain is approximately 45 kDa and anchored in the membrane. The HLA-E gene contains 8 exons. Exon one encodes the signal peptide, exons 2 and 3 encode the α1 and α2 domains, which both bind the peptide, exon 4 encodes the α3 domain, exon 5 encodes the transmembrane domain, and exons 6 and 7 encode the cytoplasmic tail.[2]
Function
HLA-E has a very specialized role in cell recognition by natural killer cells (NK cells).[3] HLA-E binds a restricted subset of peptides derived from signal peptides of classical MHC class I molecules, namely HLA-A, B, C, G.[4] These peptides are released from the membrane of the endoplasmic reticulum (ER) by the signal peptide peptidase and trimmed by the cytosolic proteasome.[5][6] Upon transport into the ER lumen by the transporter associated with antigen processing (TAP), these peptides bind to a peptide binding groove on the HLA-E molecule.[7] This allows HLA-E to assemble correctly and to be expressed on the cell surface. NK cells recognize the HLA-E+peptide complex using the heterodimeric receptor CD94/NKG2A/B/C.[3] When CD94/NKG2A or CD94/NKG2B is engaged, it produces an inhibitory effect on the cytotoxic activity of the NK cell to prevent cell lysis. However, binding of HLA-E to CD94/NKG2C (see KLRC2) results in NK cell activation. This interaction has been shown to trigger expansion of NK cell subsets in antiviral responses,[8] where adaptive NK cells that express CD94/NKG2C can specifically recognise HCMV-derived peptide antigens.[9]
References
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Further reading
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- Kuby Immunology, 6th edition, by Thomas J. Kindt, Richard A. Goldsby, and Barbara A. Kuby W. H. Freeman and Company, New York
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