Article: article from journal or magazin.
T cell affinity regulates asymmetric division, effector cell differentiation, and tissue pathology.
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
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.
Animals, Cell Differentiation, Cell Division, Cells, Cultured, Ligands, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Phenotype, Receptors, Antigen, T-Cell/immunology, T-Lymphocytes/cytology, T-Lymphocytes/immunology
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