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Immunity. 1998 Oct;9(4):565-74.

Differential roles of ERK and p38 MAP kinase pathways in positive and negative selection of T lymphocytes.

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Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Japan.


Clonal selection of T lymphocytes is essential for establishing self/non-self discrimination of immune recognition. It is known that cell surface signals such as avidity and valency of TCR-ligand interactions influence the fate of individual thymocytes, founding a primary repertoire of T cells. However, intracellular signals that govern positive and negative selection in the thymus have been unclear. The present study using the retroviral gene transfer technique shows that MKK1 activation in developing T cells is sufficient for providing positive selection signals. We also show that the MKK6-p38 signaling pathway is critically involved in inducing negative selection of thymocytes. These results suggest that intracellular signals through different MAP kinase cascades selectively guide positive and negative selection of T lymphocytes.

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