THE INFLUENCE OF THE MAPK PATHWAY ON T-CELL LINEAGE COMMITMENT

During development, progenitor thymocytes differentiate into either CD 4 or CD8 T cells, and this fate decision depends on the specificity of the T cell antigen receptor (TCR) for MHC class II or class I molecul es. Based on the mechanisms of fate specification known for simple met azoan organisms, we sought to determine whether the extracellular sign al-related kinases (ERKs) play a role in T cell differentiation and li neage commitment. Using a dominant gain-of-function mutant of the erk2 gene, we show that differentiation into the CD4 lineage is favored. W e also show that, conversely, the addition of a pharmacological inhibi tor of the ERK pathway favors differentiation into the CD8 lineage. We present a quantitative selection model that incorporates these result s as well as those of recent reports on the role of Notch in T cell li neage specification.