TCR Affinity Controls the Dynamics but Not the Functional Specification of the Antimycobacterial CD4+ T Cell Response.

Journal of immunology (Baltimore, Md. : 1950) 2021 Jun 15

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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 peptide:MHC binding affinity, we reveal that TCR affinity does not control Th1 effector function acquisition or the functional output of individual effectors following mycobacterial infection in mice. 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 binding affinity in Th1 differentiation and suggest that the temporal activation of clones with different TCR affinity is a major strategy to coordinate immune surveillance against persistent pathogens. Copyright © 2021 by The American Association of Immunologists, Inc.

Citation

Nayan D Bhattacharyya, Claudio Counoupas, Lina Daniel, Guoliang Zhang, Stuart J Cook, Taylor A Cootes, Sebastian A Stifter, David G Bowen, James A Triccas, Patrick Bertolino, Warwick J Britton, Carl G Feng. TCR Affinity Controls the Dynamics but Not the Functional Specification of the Antimycobacterial CD4+ T Cell Response. Journal of immunology (Baltimore, Md. : 1950). 2021 Jun 15;206(12):2875-2887