Protein Kinase C- Is Required for Efficient Positive Selection
نویسندگان
چکیده
Protein kinase C(PKC ) is critical for TCR-initiated signaling in mature T cells, but initial reports found no requirement for PKC in thymocyte development. Thymocytes and peripheral T cells utilize many of the same signaling components and, given the significant role of PKC in peripheral T cells, it was surprising that it was not involved at all in TCR signaling in thymocytes. We decided to re-evaluate the role of PKC in thymocyte development using the well-characterized class II-restricted n3.L2 TCR-transgenic TCR model. Analysis of n3.L2 PKC / mice revealed a defect in thymocyte-positive selection, resulting in a 50% reduction in the generation of n3.L2 CD4 single-positive thymocytes and n3.L2 CD4 mature T cells. Competition between n3.L2 WT and n3.L2 PKC / thymocytes in bone marrow chimeras revealed a more dramatic defect, with a >80% reduction in generation of n3.L2 CD4 single-positive thymocytes derived from PKC / mice. Inefficient positive selection of n3.L2 PKC / CD4 single-positive cells resulted from “weaker” signaling through the TCR and correlated with diminished ERK activation. The defect in positive selection was not complete in the PKC / mice, most likely accounted for by compensation by other PKC isoforms not evident in peripheral cells. Similar decreased positive selection of both CD4 and CD8 single-positive thymocytes was also seen in nontransgenic PKC / mice. These findings now place PKC as a key signaling molecule in the positive selection of thymocytes as well as in the activation of mature T cells. The Journal of Immunology, 2008, 181: 4696 – 4708.
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