T cell affinity regulates asymmetric division, effector cell differentiation, and tissue pathology.

ABSTRACT: 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 sy

SUBMITTER: King CG 

PROVIDER: S-EPMC3622938 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature