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J Immunol. 2014 Jan 1;192(1):200-5. doi: 10.4049/jimmunol.1302289. Epub 2013 Nov 22.

Inflammation and TCR signal strength determine the breadth of the T cell response in a bim-dependent manner.

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1
Swiss Vaccine Research Institute, 1066 Epalinges, Switzerland;

Abstract

Generating a diverse T cell memory population through vaccination is a promising strategy to overcome pathogen epitope variability and tolerance to tumor Ags. The effector and memory pool becomes broad in TCR diversity by recruiting high- and low-affinity T cells. We wanted to determine which factors dictate whether a memory T cell pool has a broad versus focused repertoire. We find that inflammation increases the magnitude of low- and high-affinity T cell responses equally well, arguing against a synergistic effect of TCR and inflammatory signals on T cell expansion. We dissect the differential effects of TCR signal strength and inflammation and demonstrate that they control effector T cell survival in a bim-dependent manner. Importantly, bim-dependent cell death is overcome with a high Ag dose in the context of an inflammatory environment. Our data define the framework for the generation of a broad T cell memory pool to inform future vaccine design.

PMID:
24273000
PMCID:
PMC3903384
DOI:
10.4049/jimmunol.1302289
[Indexed for MEDLINE]
Free PMC Article
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