Journal
IMMUNITY
Volume 37, Issue 4, Pages 709-720Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2012.06.021
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Funding
- EMBO, HSFP
- Swiss Vaccine Research Institute [310030_130512/1]
- Synergia [SNF]
- Sybilla
- EU FP7
- TerraIncognita [ERC]
- [310030B_133131/1]
- Swiss National Science Foundation (SNF) [310030_130512] Funding Source: Swiss National Science Foundation (SNF)
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The strength of interactions between T cell receptors and the peptide-major histocompatibility complex (pMHC) directly modulates T cell fitness, clonal expansion, and acquisition of effector properties. Here we show that asymmetric T cell division is an important mechanistic link between increased signal strength, effector differentiation, and the ability to induce tissue pathology. Recognition of pMHC above a threshold affinity drove responding T cells into asymmetric cell division. The ensuing proximal daughters underwent extensive division and differentiated into short-lived effector cells expressing the integrin VLA-4, allowing the activated T cell to infiltrate and mediate destruction of peripheral target tissues. In contrast, T cells activated by below-threshold antigens underwent symmetric division, leading to abortive clonal expansion and failure to fully differentiate into tissue-infiltrating effector cells. Antigen affinity and asymmetric division are important factors that regulate fate specification in CD8(+) T cells and predict the potential of a self-reactive T cell to mediate tissue pathology.
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