In the periphery, upon antigen recognition by alphabetaTCR, naïve CD4 T cells undergo functional differentiation and acquire the ability to produce a specific set of cytokines. At least four Th cell subsets, i.e., Th1, Th2, Th17 and iTreg cells have so far been identified and the differentiation of each subset is driven by distinct cytokine sets. Antigen recognition by TCR and the activation of the TCR-mediated signaling pathways that follows, however, are most critical for initiating Th cell differentiation. This review focuses on the TCR signal strength and the TCR-mediated signaling pathways that control the differentiation into these four Th cell subsets.
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