Cutting edge: TLR ligands increase TCR triggering by slowing peptide-MHC class I decay rates.
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.
Rudd
Brian D
BD
Department of Immunobiology and the Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ 85718, USA.
Brien
James D
JD
Davenport
Miles P
MP
Nikolich-Zugich
Janko
J
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology*; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000276:immunology*; D051193:Toll-Like Receptors / Q000819:agonists / Q000096:biosynthesis / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D014611:Vaccination
D015815:Cell Adhesion Molecules; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D051193:Toll-Like Receptors