SELECTIVE REQUIREMENT FOR MAP KINASE ACTIVATION IN THYMOCYTE DIFFERENTIATION

ENGAGEMENT of the T-cell receptor (TCR) with cognate ligands provokes different outcomes depending on the developmental stage of the T cell and on the properties of the ligand. In immature thymocytes TCR stimul ation may result in maturation (positive selection) or death (negative selection), whereas in mature T cells it may induce proliferation, de ath or unresponsiveness(1-5). To investigate the different signals inv olved in these processes, we have analysed the role of the MAP kinase (MAPK) cascade, which is required for growth-factor-stimulated replica tion and for differentiation in other cell types(6-9), by expressing a catalytically inactive form of MAPK kinase (MEK-1) in thymocytes, the reby blocking MAPK activation, We find that positive selection of thes e cells is inhibited but that negative selection and TCR-induced proli feration are unaffected. Our results indicate that the intracellular s ignals regulating lineage commitment in T cells parallel those in phot oreceptor cell specification in Drosophila(10) and vulval cell differe ntiation in Caenorhabditis elegans(11), suggesting that general rules for cell-type specification could apply among all metazoans.