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The self-obsession of T cells: how TCR signaling thresholds affect fate 'decisions' and effector function

2014; Nature Portfolio; Volume: 15; Issue: 9 Linguagem: Inglês

10.1038/ni.2938

1529-2916

Kristin A. Hogquist, Stephen C. Jameson,

CAR-T cell therapy research

Thymocytes and mature T cells are exposed to a broad range of self-peptides of varying reactivity with TCRs. Hogquist and Jameson discuss how differences in self-reactivity and TCR signal strength dictate subsequent cell fates. Self-reactivity was once seen as a potential characteristic of T cells that was eliminated by clonal selection to protect the host from autoimmune pathology. It is now understood that the T cell repertoire is in fact broadly self-reactive, even self-centered. The strength with which a T cell reacts to self ligands and the environmental context in which this reaction occurs influence almost every aspect of T cell biology, from development to differentiation to effector function. Here we highlight recent advances and discoveries that relate to T cell self-reactivity, with a particular emphasis on T cell antigen receptor (TCR) signaling thresholds.