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Sci. Signal., 23 March 2010
Vol. 3, Issue 114, p. pe11
[DOI: 10.1126/scisignal.3114pe11]

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Two Receptors, Two Kinases, and T Cell Lineage Determination

Balbino Alarcón* and Hisse M. van Santen

Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid 28049, Spain.

Abstract: The T cell antigen receptor (TCR) serves as a paradigm for how membrane receptors transmit signals to the cytoplasm because it controls many aspects of T cell differentiation and function by detecting atom-sized variations in the quality of the ligand that is recognized. The mechanisms that underlie the different signaling outcomes are unclear. Studies that suggest a ligand-tailored, qualitatively different signal are confronted with evidence that favors a quantitative model, and studies of TCR-dependent T cell differentiation in the thymus are no exception. Mature T cells with an {alpha}β TCR are classified according to two major distinct subsets based on the mutually exclusive presence of the co-receptors CD4 and CD8, which play essential roles in recognition of the major histocompatibility complex (MHC) class II and I ligands, respectively, and in the recruitment of the tyrosine kinase Lck to the TCR complex. Mature CD4+ and CD8+ T cells derive from a common precursor in the thymus, a double-positive (DP) thymocyte, which has both co-receptors. Early signaling models suggested that the differential capacity of CD4 and CD8 to recruit Lck to the TCR underlay lineage decision. A study now shows that differentiation into the CD8+ lineage requires the TCR-induced increased abundance of the tyrosine kinase {zeta} chain–associated protein kinase of 70 kD (Zap70). This finding, together with the known importance of Lck in the determination of CD4+ and CD8+ lineages, enables us to propose that a balance between the activation of these two kinases by the TCR determines lineage decisions.

* Corresponding author. E-mail, balarcon{at}cbm.uam.es

Citation: B. Alarcón, H. M. van Santen, Two Receptors, Two Kinases, and T Cell Lineage Determination. Sci. Signal. 3, pe11 (2010).

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