Analysis of functional sites on a peptide antigen, p43-58, in I-A or I-E-restricted T cell responses.
It has been shown that two different sites (an agretope and an epitope) on a peptide antigen function independently in T cell responses to the antigen. By virtue of these sites, antigens, MHC molecules, and TCRs constitute trimolecule complexes which eventually result in T cell activation. In our previous reports, we have defined that residues 46 and 54 on synthetic peptide composed of residues 43-58 of pigeon cytochrome c (p43-58, AEGFSYTDANKNKGIT) and its analogs function as an agretope and residue 50 as an epitope in both I-Ab and I-Ak-carrying mice. In the present study, to extend our method to the other MHC class II molecules (I-E), we used two peptide antigens, 46D50V54R and 50V54R, which had been prepared by substitution of amino acids at positions, 46, 50 and 54 or 50 and 54 of p43-58 D, V, R or V, R, respectively, and compared the immunogenicity with those of other peptide analogs. The 46D50V54R was shown to be non-immunogenic in I-Ab-carrying mice and the 50V54R was non-immunogenic in I-Ak-carrying mice. In contrast, the 46D50V54R or 50V54R could induce I-E-restricted proliferative responses of T lymphocytes in I-Eb/k- or I-Ek/k-carrying mice, respectively. Furthermore, residues 46 and 54 were shown to function as agretopes and residue 50 as an epitope in the I-E-restricted responses as they did in the I-A-restricted responses, even though some differences were seen between peptide-I-E interaction and peptide-I-A interaction. These agretopes and epitope functioned independently.
Gotohda
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Institute of Immunological Science, Hokkaido University, Japan.
Ogasawara
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Wambua
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PP
Onoé
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K
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000737:chemistry*; D001665:Binding Sites; D003574:Cytochrome c Group / Q000737:chemistry / Q000276:immunology; D000939:Epitopes / Q000737:chemistry; D000949:Histocompatibility Antigens Class II; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D003574:Cytochrome c Group; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D010455:Peptides