HLA-E (human leucocyte antigen-E) is a conserved class I major histocompatibility molecule which has only limited polymorphism. It binds to the leader peptide derived from the polymorphic classical major histocompatibility molecules HLA-A, HLA-B and HLA-C. This peptide binding is highly specific and stabilizes the HLA-E protein, allowing it to migrate to the cell surface. A functioning TAP (transporter associated with antigen processing) molecule is required to transport these peptides into the endoplasmic reticulum, where they can interact with HLA-E. HLA-E then migrates to the cell surface, where it interacts with CD94/NKG2A receptors on natural killer cells. This interaction inhibits natural killer cell-mediated lysis of a cell displaying HLA-E. If the leader peptide is not present in the endoplasmic reticulum, HLA-E is unstable and is degraded before it reaches the cell surface. In damaged cells, such as virally infected or tumour cells, down-regulation of HLA-A, HLA-B and HLA-C production or inhibition of TAP prevents stabilization of HLA-E by the leader peptide. Under these circumstances, HLA-E does not reach the cell surface and the cell is then vulnerable to lysis by natural killer cells. The molecular mechanisms underlying this function of HLA-E have been revealed by crystallographic studies of the structure of HLA-E.
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June 06 2000
Molecular basis of human natural killer cell recognition of HLA-E (human leucocyte antigen-E) and its relevance to clearance of pathogen-infected and tumour cells
Christopher A. O'CALLAGHAN
1MRC Human Immunology Unit, Nuffield Department of Clinical Medicine, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, U.K.
Correspondence: Dr C. A. O'Callaghan University of California San Francisco, Department of Microbiology and Immunology, Box 0414, 513 Parnassus Avenue, HSE 415–420, San Francisco, CA 94143-0414, U.S.A. (e-mail [email protected]).
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Publisher: Portland Press Ltd
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 99 (1): 9–17.
Citation
Christopher A. O'CALLAGHAN; Molecular basis of human natural killer cell recognition of HLA-E (human leucocyte antigen-E) and its relevance to clearance of pathogen-infected and tumour cells. Clin Sci (Lond) 1 July 2000; 99 (1): 9–17. doi: https://doi.org/10.1042/cs0990009
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