Commitment to the CD4 lineage mediated by extracellular signal-related kinase mitogen-activated protein kinase and Lck signaling

The development of T cells results in a concordance between the specificity of the TCR for MHC class I and class II molecules and the expression of CD 8 and CD4 coreceptors, Based on analogy to simple metazoan models of organ development and lineage commitment, we sought to determine whether extracel lular signal-related kinase (Erk) mitogen-activated protein (MAP) kinase pa thway signaling acts as an inductive signal for the CD4 Lineage. Here, we s how that, by altering the intracellular signaling involving the Erk/MAP kin ase pathway, T cells,vith specificity for MHC class I can be diverted to ex press CD4, and, conversely, T cells with specificity for MHC class II can b e diverted to express CD8. Furthermore, we find that activation of the sl c -family tyrosine kinase, p56(lck) is an upstream mediator of lineage commit ment. These results suggest a simple mechanism for lineage commitment in T cell development.