Activation thresholds determine susceptibility to peptide-induced tolerance in a heterogeneous myelin-reactive T cell repertoire

D McCue, KR Ryan, DC Wraith, SM Anderton

Research output: Contribution to journalArticle (Academic Journal)peer-review

15 Citations (Scopus)

Abstract

Altered peptide ligands (APL) with increased MHC-binding properties are highly effective at inducing T cell tolerance after systemic administration in soluble form, preventing experimental autoimmune encephalomyelitis (EAE) induced with the myelin basic protein (MBP) Ac1-9 peptide. We have previously described a diverse Ac1-9-reactive T cell repertoire with differing TCR affinities. A remaining question is what proportion of this repertoire is silenced by peptide therapy? Here, we show that the sensitivity of a T cell to peptide-induced tolerance is related to its avidity for native Ac1-9. These data provide new evidence that self-reactive T cells bearing low-affinity TCRs are able to escape therapeutic induction of tolerance.
Translated title of the contributionActivation thresholds determine susceptibility to peptide-induced tolerance in a heterogeneous myelin-reactive T cell repertoire
Original languageEnglish
Pages (from-to)96 - 106
Number of pages11
JournalJournal of Neuroimmunology
Volume156
Publication statusPublished - 2004

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