Abstract
Abstract In the lymph node, T cells can receive signals through the recognition of pMHC during both long-lived (>5 minutes) synapses or short-lived (<5 minutes) kinapses with antigen presenting cells (APC). It has been shown that injection of low dose antigenic peptide can lead to T cell tolerance and T regulatory cells induction in vivo. Here, we are evaluating the impact of MHC-peptide potency, peptide dose and APC frequency on induction of tolerance and Treg in relation to the dynamics of T cell-antigen presenting cell (APC) interactions. We hypothesize that induction of tolerance will be a function of signal integration by T cells and that the formation of synapses will favor tolerance induction when the frequency of APC is low based on the ability of rare APC to capture T cells with MHC-peptide potency and dose supporting synapse formation. In vitro, the high potency MHC-peptide has an advantage over the low potency MHC-peptide for Treg induction when APC frequency is low. In vivo, the low potency MHC-peptide induces Treg and tolerance through kinapses. We are now in the process of characterizing, in vivo, the tolerance and Treg induction in condition where the number of APC is limited using a mixed bone marrow chimera approach.
Published Version
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