T cell recognition of MHC class II-associated peptides is independent of peptide affinity for MHC and sodium dodecyl sulfate stability of the peptide/MHC complex. Effects of conservative amino acid substitutions at anchor position 1 of influenza matrix protein19-31.
T cells recognize peptide fragments of Ags bound to MHC-encoded molecules. Pockets in the MHC peptide-binding groove accommodate a limited set of amino acid side chains present at anchor positions in peptide; however, the functional significance of accommodation of different side chains at an anchor position in peptide is not clear. A panel of T cell clones was evaluated to test the effect of conservative amino acid substitution at a primary peptide anchor position. Results of T cell stimulation studies were correlated with two well studied characteristics of the peptide/MHC complex, which are the affinity of peptide binding to MHC and the stability of the resulting complex upon PAGE in the presence of SDS. We found that formation of a functional complex required neither high affinity peptide binding nor SDS stability. Furthermore, T cell clones differed in their ability to recognize individual peptide variants, suggesting that some structural aspect of the peptide/MHC complex is influenced by interactions between peptide anchor residues and MHC pockets.
Wu
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S
Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee 53201, USA.
Gorski
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Eckels
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Newton-Nash
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DK
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry* / Q000276:immunology*; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D006684:HLA-DR Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D000596:Amino Acids; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010455:Peptides; D014763:Viral Matrix Proteins; D012967:Sodium Dodecyl Sulfate