Hydrophobic strip-of-helix algorithm for selection of T cell-presented peptides.
In extension of the hypothesis that an amphipathic alpha helix of Ii (Phe146-Val164) bound to the foreign antigen-presenting site (desetope) of class II MHC molecules through hydrophobic amino acid residues (Phe146, Leu150, Leu153, Met157, Ile160, Val164) which were present in an axial strip along one side of the Ii helix, we developed an algorithm to search for T cell-presented peptides showing a similar hydrophobic strip-of-helix. Such peptides might bind to the class II MHC molecule site which was complementary to the Ii hydrophobic strip-of-helix. The strip-of-helix hydrophobicity index was the mean hydrophobicity (from Kyte-Doolittle values) of sets of amino acids in axial strips down sides of helices for 3-6 turns, at positions, n, n + 4, N + 7, n + 11, n + 14, and n + 18. Peptides correlating well with T cell responsiveness had: (1) 12-19 amino acids (3-5 cycles or 4-6 turns of an alpha helix), (2) a strip with highly hydrophobic residues, (3) adjacent, moderately hydrophilic strips, and (4) no prolines. The degree of hydrophilicity of the remainder of a putative antigenic helix above a threshold value did not count in this index. That is, the magnitude of amphipathicity was not judged to be the principal selecting factor for T cell-presented peptides. This simple algorithm to quantitate strip-of-helix hydrophobicity in a putative amphipathic alpha helix, allowing otherwise generally hydrophilic residues, predicted 10 of 12 T cell-presented peptides in seven well-studied proteins. The derivation and application of this algorithm were analyzed.
Stille
C J
CJ
Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655-2397.
Thomas
L J
LJ
Reyes
V E
VE
Humphreys
R E
RE
D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology*; D003574:Cytochrome c Group / Q000276:immunology; D009113:Muramidase / Q000276:immunology; D009211:Myoglobin / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D003574:Cytochrome c Group; D009211:Myoglobin; D010455:Peptides; D010047:Ovalbumin; D009113:Muramidase