Critical role of an amino acid residue in a T cell determinant is due to its interaction with a neighboring non-critical residue.
Several lines of evidence support the concept of two functionally distinct sites on antigen: the epitope, involved in interaction with the T cell receptor and the agretope, interacting with Ia. We investigated the Ia and T cell receptor interaction sites on the synthetic polypeptide antigen poly-18 [poly-EYK(EYA)5] using T cell hybridoma clones specific for this antigen in the context of I-Ad. Peptides with amino acid sequences related to poly-18 were synthesized. These were used to identify the critical residues in the minimum peptide sequence required for activation. Clone A.1.1 responds to the minimal peptide EYK(EYA)4 but not to (EYA)5. This identifies Lys3 as a critical amino acid for this hybridoma. Surprisingly, the substituted peptide EYAEAA(EYA)3 could activate A.1.1, indicating that an Ala at position 5 instead of a Tyr obviates the critical requirement for Lys3. This demonstrates that the function of critical residues may extend beyond contacting the T cell receptor or Ia, to include a third role: that of interacting with other amino acids of the T cell epitope, thus influencing the antigen's recognition by T cells.
Boyer
M
M
Department of Immunology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Novak
Z
Z
Fotedar
A
A
Fraga
E
E
Singh
B
B
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D000939:Epitopes; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D000596:Amino Acids; D000939:Epitopes; D011948:Receptors, Antigen, T-Cell