Details

Autor(en) / Beteiligte

• King, Carolyn G.
• Koehli, Sabrina
• Hausmann, Barbara
• Schmaler, Mathias
• Zehn, Dietmar
• Palmer, Ed

Titel

T Cell Affinity Regulates Asymmetric Division, Effector Cell Differentiation, and Tissue Pathology

Ist Teil von

• Immunity (Cambridge, Mass.), 2012-10, Vol.37 (4), p.709-720

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. ► Antigens above a specific affinity threshold induce asymmetric T cell division ► Proximal daughter T cells efficiently differentiate into tissue-infiltrating SLECs ► Below-threshold antigens induce symmetric division and few tissue infiltrating SLECs