TCR affinity controls the dynamics but not the functional specification of the Th1 response to mycobacteria
Bhattacharyya, N. D.; Counoupas, C.; Daniel, L.; Zhang, G.; Cook, S. J.; Cootes, T. A.; Stifter, S. A.; Bowen, D. G.; Bertolino, P.; Britton, W. J.; Feng, C. G.
Show abstract
The quality of T cell responses depends on the lymphocytes ability to undergo clonal expansion, acquire effector functions and traffic to the site of infection. Although TCR signal strength is thought to dominantly shape the T cell response, by using TCR transgenic CD4+ T cells with different pMHC binding affinity, we reveal that TCR affinity does not control Th1 effector function acquisition nor the functional output of individual effectors following mycobacterial infection. Rather, TCR affinity calibrates the rate of cell division to synchronize the distinct processes of T cell proliferation, differentiation and trafficking. By timing cell division-dependent IL-12R expression, TCR affinity controls when T cells become receptive to Th1-imprinting IL-12 signals, determining the emergence and magnitude of the Th1 effector pool. These findings reveal a distinct yet cooperative role for IL-12 and TCR signalling in Th1 differentiation and suggests that the temporal activation of clones with different TCR affinity is a major strategy to coordinate immune surveillance against persistent pathogens.
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