title: Functional degeneracy of residues in a T cell peptide epitope contributes to its recognition by different T cell hybridomas.
abstract: Synthetic antigen Poly EYK(EYA)5 induces T cells of narrowly defined fine specificity as represented by the two I-Ad-restricted T cell hybridomas, A.1.1 and B.1.1. Both these hybridomas recognize the minimum 15-amino-acid peptide sequence EYK(EYA)4. We have characterized the residues involved in the recognition of EYK(EYA)4 peptide by these hybridomas with synthetic peptides and discovered a distinct functional hierarchy for the residues in the sequence. Even with the repeating tripeptide (EYA)5, which is recognized by B.1.1 cells, the residues that are essential cluster near the middle of the sequence but not near the N- or C-terminal region. Different MHC binding and TCR contacting residues were found for each of the hybridomas. The results suggest that different T cells either recognize different parts of the peptide MHC complex or that the peptide binds to MHC in multiple conformations. This was supported by the fact that Poly EYK(EYA)5 is alpha-helical but the peptides used here showed only a slight propensity to adopt this structure and it did not correlate with their functional activity. We also found that (EYA)5 does not compete with EYK(EYA)4 in the stimulation of A.1.1 cells despite its obvious capacity to interact with I-Ad when it stimulates B.1.1 cells. This may be because these peptides have a low affinity for Ia and therefore only appropriate TCR interactions would stabilize the antigen-Ia complex. In conclusion, antigen-MHC-TCR interaction appears to be a dynamic process which allows recognition of different residues of a T cell determinant by different T cells.
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Boyer
authors.forename: Z
authors.initials: Z
authors.lastname: Novak
authors.forename: E
authors.initials: E
authors.lastname: Fraga
authors.forename: K
authors.initials: K
authors.lastname: Oikawa
authors.forename: C M
authors.initials: CM
authors.lastname: Kay
authors.forename: A
authors.initials: A
authors.lastname: Fotedar
authors.forename: B
authors.initials: B
authors.lastname: Singh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006825:Hybridomas / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000941:Antigens; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell