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Critical role of an amino acid residue in a T cell determinant is due to its interaction with a neighboring non‐critical residue
Author(s) -
Boyer Michel,
Novak Zuzana,
Fotedar Arun,
Fraga Ester,
Singh Bhagirath
Publication year - 1990
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830200939
Subject(s) - residue (chemistry) , biology , amino acid residue , amino acid , biochemistry , stereochemistry , peptide sequence , chemistry , gene
Abstract 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‐A d . 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 Lys 3 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 Lys 3 . 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.