T-cell antagonism by short half-life pMHC ligands can be mediated by an efficient trapping of T-cell polarization toward the APC

Leandro J. Carreño, Erick M. Riquelme, Pablo A. González, Nicolas Espagnolle, Claudia A. Riedel, Salvatore Valitutti, Alexis M. Kalergis

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

20 Citas (Scopus)

Resumen

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 toward the APC interface. 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. However, whether the half-life of the TCR/pMHC interaction can modulate the efficiency of T-cell secretory machinery polarization toward an APC still remains unclear. Here, by using altered peptide ligands 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 although 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.

Idioma originalInglés
Páginas (desde-hasta)210-215
Número de páginas6
PublicaciónProceedings of the National Academy of Sciences of the United States of America
Volumen107
N.º1
DOI
EstadoPublicada - 2010

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