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The Influence of the MAPK Pathway on T Cell Lineage Commitment

1997; Cell Press; Volume: 7; Issue: 5 Linguagem: Inglês

10.1016/s1074-7613(00)80382-9

1097-4180

Leslie L. Sharp, David Schwarz, Cynthia M. Bott, Christopher J. Marshall, Stephen Μ. Hedrick,

Invertebrate Immune Response Mechanisms

During development, progenitor thymocytes differentiate into either CD4 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 molecules. Based on the mechanisms of fate specification known for simple metazoan organisms, we sought to determine whether the extracellular signal-related kinases (ERKs) play a role in T cell differentiation and lineage commitment. Using a dominant gain-of-function mutant of the erk2 gene, we show that differentiation into the CD4 lineage is favored. We also show that, conversely, the addition of a pharmacological inhibitor of the ERK pathway favors differentiation into the CD8 lineage. We present a quantitative selection model that incorporates these results as well as those of recent reports on the role of Notch in T cell lineage specification.