TY - JOUR
T1 - Cutting edge
T2 - TLR ligands increase TCR triggering by slowing peptide-MHC class I decay rates
AU - Rudd, Brian D.
AU - Brien, James D.
AU - Davenport, Miles P.
AU - Nikolich-Žugich, Janko
PY - 2008
Y1 - 2008
N2 - TLR ligands are among the key stimuli driving the optimal dendritic cell (DC) maturation critical for strong and efficacious T cell priming. In this study, we show that part of this effect occurs via increased TCR triggering. Pretreatment of DCs with TLR ligands resulted in the triggering of many more TCRs in responding CD8+ T cells. Importantly, even when DCs expressed the same amount of cognate peptide-MHC (pMHC) molecules, TLR ligand treatment resulted in down-regulation of larger numbers of TCR molecules. This was independent of the up-regulation of costimulatory, adhesion or cytokine molecules or the amount of noncognate pMHCs. Rather, DCs pretreated with TLR ligands exhibited increased stability of cognate pMHCs, enabling extended TCR triggering. These findings are of potential importance to T cell vaccination.
AB - TLR ligands are among the key stimuli driving the optimal dendritic cell (DC) maturation critical for strong and efficacious T cell priming. In this study, we show that part of this effect occurs via increased TCR triggering. Pretreatment of DCs with TLR ligands resulted in the triggering of many more TCRs in responding CD8+ T cells. Importantly, even when DCs expressed the same amount of cognate peptide-MHC (pMHC) molecules, TLR ligand treatment resulted in down-regulation of larger numbers of TCR molecules. This was independent of the up-regulation of costimulatory, adhesion or cytokine molecules or the amount of noncognate pMHCs. Rather, DCs pretreated with TLR ligands exhibited increased stability of cognate pMHCs, enabling extended TCR triggering. These findings are of potential importance to T cell vaccination.
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U2 - 10.4049/jimmunol.181.8.5199
DO - 10.4049/jimmunol.181.8.5199
M3 - Article
C2 - 18832671
AN - SCOPUS:54049103221
SN - 0022-1767
VL - 181
SP - 5199
EP - 5203
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -