Peptide binding characteristics of the non-classical class Ib MHC molecule HLA-E assessed by a recombinant random peptide approach.
BACKGROUND
Increasing evidence suggests that the effect of HLA-E on Natural Killer (NK) cell activity can be affected by the nature of the peptides bound to this non-classical, MHC class Ib molecule. However, its reduced cell surface expression, and until recently, the lack of specific monoclonal antibodies hinder studying the peptide-binding specificity HLA-E.


RESULTS
An in vitro refolding system was used to assess binding of recombinant HLA-E to either specific peptides or a nonamer random peptide library. Peptides eluted from HLA-E molecules refolded around the nonamer library were then used to determine a binding motif for HLA-E. Hydrophobic and non-charged amino acids were found to predominate along the peptide motif, with a leucine anchor at P9, but surprisingly there was no methionine preference at P2, as suggested by previous studies.


CONCLUSIONS
Compared to the results obtained with rat classical class Ia MHC molecules, RT1-A1c and RT1-Au, HLA-E appears to refold around a random peptide library to reduced but detectable levels, suggesting that this molecule's specificity is tight but probably not as exquisite as has been previously suggested. This, and a previous report that it can associate with synthetic peptides carrying a viral sequence, suggests that HLA-E, similar to its mouse counterpart (Qa-1b), could possibly bind peptides different from MHC class I leader peptides and present them to T lymphocytes.
Stevens
J
J
Laboratory of Functional Immunogenetics, The Babraham Institute, Cambridge CB2 4AT, UK. jstevens@scripps.edu
Joly
E
E
Trowsdale
J
J
Butcher
G W
GW
D020816:Amino Acid Motifs; D001665:Binding Sites; D003001:Cloning, Molecular; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D000097625:HLA-E Antigens
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D019151:Peptide Library; D010455:Peptides; D000097625:HLA-E Antigens