| First Author | Zehn D | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 1 | Pages | 200-5 |
| PubMed ID | 24273000 | Mgi Jnum | J:207098 |
| Mgi Id | MGI:5554463 | Doi | 10.4049/jimmunol.1302289 |
| Citation | Zehn D, et al. (2014) Inflammation and TCR signal strength determine the breadth of the T cell response in a bim-dependent manner. J Immunol 192(1):200-5 |
| abstractText | 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. |