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T Cells Integrate Local and Global Cues to Discriminate between Structurally Similar Antigens

Abstract : T lymphocytes' ability to discriminate between structurally related antigens has been attributed to the unique signaling properties of the T cell receptor. However, recent studies have suggested that the output of this discrimination process is conditioned by environmental cues. Here, we demonstrate how the IL-2 cytokine, collectively generated by strongly activated T cell clones, can induce weaker T cell clones to proliferate. We identify the PI3K pathway as being critical for integrating the antigen and cytokine responses and for controlling cell-cycle entry. We build a hybrid stochastic/deterministic computational model that accounts for such signal synergism and demonstrates quantitatively how T cells tune their cell-cycle entry according to environmental cytokine cues. Our findings indicate that antigen discrimination by T cells is not solely an intrinsic cellular property but rather a product of integration of multiple cues, including local cues such as antigen quality and quantity, to global ones like the extracellular concentration of inflammatory cytokines.
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Submitted on : Friday, October 2, 2015 - 12:45:47 PM
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Guillaume Voisinne, Briana G Nixon, Anna Melbinger, Georg Gasteiger, Massimo Vergassola, et al.. T Cells Integrate Local and Global Cues to Discriminate between Structurally Similar Antigens. Cell Reports, Elsevier Inc, 2015, ⟨10.1016/j.celrep.2015.04.051⟩. ⟨hal-01208299⟩

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