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 contribution||Activation thresholds determine susceptibility to peptide-induced tolerance in a heterogeneous myelin-reactive T cell repertoire|
|Pages (from-to)||96 - 106|
|Number of pages||11|
|Journal||Journal of Neuroimmunology|
|Publication status||Published - 2004|