Strengthening A Weak Choice

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Science  24 Nov 2006:
Vol. 314, Issue 5803, pp. 1219
DOI: 10.1126/science.314.5803.1219b

The cell surface co-receptors CD8 and CD4 define two classes of T cells and facilitate the recognition of antigens presented by the class I and class II major histocompatibility complex (MHC) proteins, respectively. They are also critical in the development and selection of T cells in the thymus. One model proposes that in double-positive thymocytes (those expressing both CD4 and CD8), the stronger signals delivered by CD4 direct T cells toward a single positive CD4 fate, whereas weaker signals emanating from CD8 contribute to class I recognition, resulting in a program of continued CD8 expression and loss of CD4. Erman et al. generated transgenic mice in which a chimeric CD8 protein carrying the intracellular CD4 domain was expressed under the normal CD8 regulatory elements. The increase in signal strength via the co-receptors in class I-restricted thymocytes did not alter lineage choice; rather, an increase in the number of cells entering the single positive CD8 T cell pool was seen. Hence, the more potent (in terms of downstream Lck kinase activation) intracellular CD4 domain could explain the familiar bias in the number of CD4 over CD8 T cells seen in the mammalian thymus. — SJS

J. Immunol. 177, 6613 (2006).

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