title: Inflammation and TCR signal strength determine the breadth of the T cell response in a bim-dependent manner.
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.
authors.affiliation: Swiss Vaccine Research Institute, 1066 Epalinges, Switzerland;
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zehn
authors.forename: Sarah
authors.initials: S
authors.lastname: Roepke
authors.forename: Kristin
authors.initials: K
authors.lastname: Weakly
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bevan
authors.forename: Martin
authors.initials: M
authors.lastname: Prlic
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell