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TLR2 Engagement on CD8 T Cells Enables Generation of Functional Memory Cells in Response to a Suboptimal TCR Signal¹

Blandine C. Mercier^2,*,,, Anne Cottalorda^2,*,,, Charles-Antoine Coupet^*,,, Jacqueline Marvel^*,, and Nathalie Bonnefoy-Bérard^3,*,,

^* Université de Lyon, Lyon, France; Institut National de la Santé et de la Recherche Médicale, Unité 851, Lyon, France; and Université Lyon1, Lyon, France

TLR are involved in the detection of microbial infection as well as endogenous ligands that signal tissue and cell damage in mammals. This recognition plays an essential role in innate immune response and the initiation of adaptive immune response. We have previously shown that murine CD8 T cells express TLR2, and that costimulation of Ag-activated CD8 T cells with TLR2 ligands enhances their proliferation, survival, and effector functions. We also demonstrated that TLR2 engagement on CD8 T cells significantly reduces their need for costimulatory signals delivered by APC. We show in this study that TLR2 engagement on CD8 T cells lowers the Ag concentration required for optimal activation, and converts a partial activation into a productive process leading to a significant expansion of cells. Using altered peptide ligands, we demonstrate that TLR2 engagement increases CD8 T cell activation and enables the generation of functional memory cells in response to a low TCR signal. This increased activation is associated with an augmented activation of the PI3K. Taken together, our results demonstrate that TLR2 engagement on CD8 T cells lowers their activation threshold for TCR signal strength and enables efficient memory cell generation in response to a weak TCR signal.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by institutional grants from Institut National de la Santé et de la Recherche Médicale and Université Claude Bernard Lyon I, and additional support from Association pour la Recherche sur le Cancer, Rhône-Alpes Region, and Cancéropole National. B.C.M. and C.-A.C. are supported by a fellowship from the French Education and Research Ministry, and A.C. was supported by a fellowship from the French Education and Research Ministry and currently by a fellowship from the Association pour la Recherche sur le Cancer.

² B.C.M. and A.C. made equal contribution to this work.

³ Address correspondence and reprint requests to Dr. Nathalie Bonnefoy-Bérard, Institut National de la Santé et de la Recherche Médicale, Unité 851, 21 Avenue Tony Garnier, 69365 Lyon Cedex 07, France. E-mail address: nathalie.bonnefoy-berard{at}inserm.fr

⁴ Abbreviations used in this paper: Pam, Pam₃CysSK₄; DC, dendritic cell; GP, glycoprotein; LCMV, lymphocytic choriomeningitis virus; MALP-2, macrophage-activating lipopeptide-2; NP, nucleoprotein; PKB, protein kinase B; KLRG1: killer cell lectin-like receptor G1.

⁵ The online version of this article contains supplemental material.