DIFFERENTIAL ROLES OF ERK AND P38 MAP KINASE PATHWAYS IN POSITIVE ANDNEGATIVE SELECTION OF T-LYMPHOCYTES

Clonal selection of T lymphocytes is essential for establishing self/n on-self discrimination of immune recognition. It is known that cell su rface signals such as avidity and valency of TCR-ligand interactions i nfluence the fate of individual thymocytes, founding a primary reperto ire of T cells. However, intracellular signals that govern positive an d negative selection in the thymus have been unclear. The present stud y using the retroviral gene transfer technique shows that MKK1 activat ion in developing T cells is sufficient for providing positive selecti on signals. We also show that the MKK6-p38 signaling pathway is critic ally involved in inducing negative selection of thymocytes. These resu lts suggest that intracellular signals through different MAP kinase ca scades selectively guide positive and negative selection of T lymphocy tes.