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  • Title: Activation thresholds determine susceptibility to peptide-induced tolerance in a heterogeneous myelin-reactive T cell repertoire.
    Author: McCue D, Ryan KR, Wraith DC, Anderton SM.
    Journal: J Neuroimmunol; 2004 Nov; 156(1-2):96-106. PubMed ID: 15465600.
    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.
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