A novel form of T cell antagonism by trapping of immunological synapse (106.49)

Abstract

Abstract T cell activation results from productive T cell receptor (TCR) engagement by a cognate peptide-MHC (pMHC) complex on the antigen presenting cell (APC) surface, a process leading to the polarization of the T cell secretory machinery towards the interface of APC. We have previously shown that the half-life of the TCR/pMHC interaction and the density of pMHC on the APC are two parameters determining T cell activation. Here, by using APLs conferring different half-lives to the TCR/pMHC interaction we have tested how this parameter can control T cell polarization. We observed that only TCR/pMHC interactions with intermediate half-lives can promote the assembly of synapses that lead to T cell activation. Strikingly, intermediate half-life interactions can be competed out by short half-life interactions, which can efficiently promote T cell polarization and antagonize T cell activation that was induced by activating intermediate half-life interactions. However, short TCR/pMHC interactions fail at promoting phosphorylation of signaling molecules at the T cell-APC contact interface, which are needed for T cell activation. Our data suggest that while intermediate half-life pMHC ligands promote assembly of activating synapses, this process can be inhibited by short half-life antagonistic pMHC ligands, which promote the assembly of non activating synapses.