HLA class I histocompatibility antigen, alpha chain E (HLA-E) also known asMHC class I antigen E is aprotein that in humans is encoded by theHLA-Egene.[5] The human HLA-E is a non-classicalMHC 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 calledQa-1b, officially known as H2-T23.
Like otherMHC 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 8exons. Exon one encodes thesignal 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 thetransmembrane domain, and exons 6 and 7 encode the cytoplasmic tail.[6]
HLA-E has a very specialized role in cell recognition bynatural killer cells (NK cells).[7] HLA-E binds a restricted subset of peptides derived fromsignal peptides of classical MHC class I molecules, namely HLA-A, B, C, G.[8] These peptides are released from the membrane of theendoplasmic reticulum (ER) by thesignal peptide peptidase and trimmed by the cytosolicproteasome.[9][10] Upon transport into the ER lumen by thetransporter associated with antigen processing (TAP), these peptides bind to a peptide binding groove on the HLA-E molecule.[11] This allows HLA-E to assemble correctly and to be expressed on thecell surface. NK cells recognize the HLA-E+peptide complex using the heterodimeric receptorCD94/NKG2A/B/C.[7] 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 (seeKLRC2) results in NK cell activation. This interaction has been shown to trigger expansion of NK cell subsets in antiviral responses,[12] whereadaptive NK cells that express CD94/NKG2C can specifically recogniseHCMV-derived peptide antigens.[13]
^abBraud VM, Allan DS, O'Callaghan CA, Söderström K, D'Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI, Phillips JH, Lanier LL, McMichael AJ (Feb 1998). "HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C".Nature.391 (6669):795–9.Bibcode:1998Natur.391..795B.doi:10.1038/35869.PMID9486650.S2CID4379457.
^Hammer Q, Rückert T, Borst EM, Dunst J, Haubner A, Durek P, Heinrich F, Gasparoni G, Babic M, Tomic A, Pietra G, Nienen M, Blau IW, Hofmann J, Na IK, Prinz I, Koenecke C, Hemmati P, Babel N, Arnold R, Walter J, Thurley K, Mashreghi MF, Messerle M, Romagnani C (May 2018). "Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells".Nature Immunology.19 (5):453–463.doi:10.1038/s41590-018-0082-6.PMID29632329.S2CID4718187.
Jensen PE, Sullivan BA, Reed-Loisel LM, Weber DA (Jun 2004). "Qa-1, a nonclassical class I histocompatibility molecule with roles in innate and adaptive immunity".Immunologic Research.29 (1–3):81–92.doi:10.1385/IR:29:1-3:081.PMID15181272.S2CID29282633.
