Modifications of Peptide Ligands Enhancing T Cell Responsiveness Imply Large Numbers of Stimulatory Ligands for Autoreactive T Cells

Marco Vergelli, Bernhard Hemmer, Matthias Kalbus, Anne B. Vogt, Nick Ling, Paul Conlon, John E. Coligan, Henry McFarland, Roland Martin

Research output: Contribution to journalArticle

Abstract

In this report, we demonstrate for autoreactive T cell clones that single amino acid modifications of the antigenic ligand can result in not only abrogated, decreased, or unmodified, but also increased, T cell responsiveness (superagonist ligands). We further studied the effects of combinations of multiple substitutions with different effects in single peptides. Experiments with peptides carrying multiple amino acid exchanges revealed that the final outcome of TCR ligation by a given ligand is the integration of negative, neutral, and positive effects of each single residue. In addition, the introduction of superagonist substitutions together with nonconservative modifications of primary and secondary TCR contacts resulted in stimulatory ligands. These findings indicate that: 1) the specificity of a single TCR is highly degenerate; 2) ligands exist for autoreactive T cells that have higher agonist activity than the autoantigen itself; 3) the rules to search for cross-reactive epitopes in autoimmunity should take into account that amino acids at certain positions within an antigenic peptide may exert superagonist activity and compensate for the negative effects of residues at other positions that would otherwise not be tolerated.

Original languageEnglish (US)
Pages (from-to)3746-3752
Number of pages7
JournalJournal of Immunology
Volume158
Issue number8
StatePublished - Apr 15 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Vergelli, M., Hemmer, B., Kalbus, M., Vogt, A. B., Ling, N., Conlon, P., Coligan, J. E., McFarland, H., & Martin, R. (1997). Modifications of Peptide Ligands Enhancing T Cell Responsiveness Imply Large Numbers of Stimulatory Ligands for Autoreactive T Cells. Journal of Immunology, 158(8), 3746-3752.