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Delgado P, Fernandez E, Dave V, Kappes D, Alarcon B
CD3 delta couples T-cell receptor signalling to ERK activation and thymocyte positive selection
Nature (2000) 406:426-430.
Abstract
Thymocytes from mice lacking the CD3 delta chain of the T-cell receptor (TCR), unlike those of other CD3-deficient mice(1,2), progress from a CD4(-)CD8(-) double-negative to a CD4(+)CD8(+) double-positive stage. However, CD3 delta(-/-) double-positive cells fail to undergo positive selection, by which double- positive cells differentiate into more mature thymocytes(3). Positive selection is also impaired in mice expressing inactive components of the Ras/mitogen activated protein (MAP) kinase signalling pathway(4-6). Here we show that CD3 delta(-/-) thymocytes are defective in the induction of extracellular signal-regulated protein kinase (ERK) MAP kinases upon TCR engagement, whereas activation of other MAP kinases is unaffected. The requirement for CD3d maps to its extracellular or transmembrane domains, or both, as expression of a tail-less CD3d rescues both ERK activation and positive selection in CD3 delta(-/-) mice. Furthermore, the defect correlates with severely impaired tyrosine phosphorylation of the linker protein LAT, and of the CD3 zeta chain that is localized to membrane lipid rafts upon TCR engagement. Our data indicate that the blockade of positive selection of CD3 delta(-/-) thymocytes may derive from defective tyrosine phosphorylation of CD3z in lipid rafts, resulting in impaired activation of the LAT/Ras/ERK pathway.
Note
Publication Date: 2000-07-27.
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