Selection of class I MHC-restricted peptides with the strip-of-helix hydrophobicity algorithm.
A strip-of-helix hydrophobicity algorithm to predict class II MHC-restricted peptides, on the basis of their structural similarity to an amphipathic, alpha-helix in Ii, also predicted peptides which were presented to cytotoxic T-cells by class I MHC molecules. This algorithm ranked peptides according to mean Kyte-Doolittle hydrophobicity values of amino acids at positions n, n + 4, n + 7, n + 11, n + 14 and n + 18 in a sequence which when coiled as a putative alpha-helix, had the indicated residues in an axial strip along one side of the helix. Sequences selected for highly scoring, hydrophobic strips were required to have at least 1 of the 4 adjacent strips scoring more negatively than -1 in the strip-of-helix hydrophobicity index and the entire sequence could contain no prolines. This algorithm predicted the class I MHC-restricted, T-cell-presented peptides in sequences of 4 proteins from which some class I MHC-restricted, T-cell-presented sequences had been experimentally determined. Since both class I and class II MHC-restricted peptides could be identified with this algorithm, one can propose that: (1) foreign peptide-binding sites (desetopes) of the class I and class II MHC molecules are structurally similar; and (2) any one T-cell-presented peptide can be presented by some specific allele of both a class I and a class II MHC antigen.
Reyes
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Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655.
Chin
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Humphreys
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D000465:Algorithms; D000595:Amino Acid Sequence; D005805:Genes, MHC Class I; D015236:HLA-C Antigens / Q000235:genetics; D006388:Hemagglutinins / Q000235:genetics; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics; D010455:Peptides / Q000235:genetics*; D016601:RNA-Binding Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
D015236:HLA-C Antigens; C038653:HLA-C*03 antigen; D006388:Hemagglutinins; C031540:M-protein, influenza virus; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010455:Peptides; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins