Differential activation of human autoreactive T cell clones by altered peptide ligands derived from myelin basic protein peptide (87-99)

Marco Vergelli, Bernhard Hemmer, Ursula Utz, Anne Vogt, Matthias Kalbus, Laura Tranquill, Paul Conlon, Nicholas Ling, Lawrence Steinman, Henry F. McFarland, Roland Martin

Research output: Contribution to journalArticlepeer-review

Abstract

We have examined the functional consequences induced by interaction of DR2a-restricted myelin basic protein (MBP) (87-99)-specific T cell clones (TCC) with altered peptide ligands (APL) derived from MBP peptide (87-99). The immunodominant MBP peptide (87-99) has been implicated as a candidate antigen in multiple sclerosis (MS) by several lines of evidence. In the present study, we have defined the T cell receptor (TCR) contact residues for DR2a-restricted, (87-99)-specific T helper type 1 T cells to design APL suitable to modify the functions of such T cells potentially relevant for the pathogenesis of MS. We show that neutral (L-alanine substitutions) or conservative exchanges of the primary and secondary TCR contact residues lead to various alterations of T cell function, ranging from differences in interleukin-2 receptor up-regulation to anergy induction and TCR antagonism. The potential usefulness of APL as an immunomodulating therapy for DR2+ MS patients is discussed.

Original languageEnglish (US)
Pages (from-to)2624-2634
Number of pages11
JournalEuropean Journal of Immunology
Volume26
Issue number11
DOIs
StatePublished - 1996
Externally publishedYes

Keywords

  • Altered peptide ligands
  • Autoimmunity
  • Human
  • Myelin basic protein
  • T lymphocyte

ASJC Scopus subject areas

  • Immunology

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