Class I cross-restricted T cells reveal low responder allele due to processing of viral antigen.
Cytotoxic T lymphocytes (CTL) recognize protein antigens which have been processed by the target cell and then presented in association with the relevant class I molecule of the major histocompatibility complex (MHC). Short synthetic peptides, which are able to associate directly with target cells, may substitute for these processed fragments in stimulating antigen-specific CTL responses. Using this approach, a dominant HLA-A2-restricted epitope has previously been mapped to residues 58-68 of influenza A virus matrix protein. Here we report HLA-A2-restricted CTL which are also able to recognize this short synthetic peptide in association with HLA-Aw69, but which fail to recognize HLA-Aw69 expressing cells infected with influenza A virus. Furthermore, individuals possessing HLA-Aw69 who respond to influenza A virus, do not respond to M58-68. These results imply that the low response to this epitope on infection of HLA-Aw69 individuals with influenza A is due to failure of the naturally processed product of matrix protein to associate with Aw69.
Bodmer
H C
HC
Institute for Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Gotch
F M
FM
McMichael
A J
AJ
D000483:Alleles; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000235:genetics*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D005805:Genes, MHC Class I; D015234:HLA-A Antigens / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology*
D000956:Antigens, Viral; D015234:HLA-A Antigens