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

Publication Type:

Journal Article

Source:

Journal of immunology (Baltimore, Md. : 1950), Volume 192, Issue 1, p.200-5 (2014)

Keywords:

2013, January 2014, Vaccine and Infectious Disease Division

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.