Control of T cell development by non-receptor protein tyrosine kinases

Abstract

Stimulation of the T cell antigen receptor leads to several possible outcomes. This is especially true in thymocytes, where ligand occupancy of the receptor may promote survival or provoke cell death. Insight into the circuitry of T cell receptor signalling has been achieved in transgenic mouse model systems. In particular, two SRC-family protein tyrosine kinases, p59fyn and p56lck, have been shown to participate in controlling mature thymocyte proliferation and immature thymocyte development, respectively. Analysis of the function of p56lck has been especially instructive and has yielded data consistent with a model in which this kinase serves as the gatekeeper at a developmental checkpoint wherein T cell receptor beta chain synthesis promotes maturation and cell division. In addition, a remarkably coherent data set supports the view that p56lck regulates allelic exclusion at the T cell receptor beta locus. Further testing of putative signalling molecules in transgenic mice promises to permit elucidation of the biochemical distinctions between positively and negatively selecting stimulation pathways active during T cell development.