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T-cell receptor ligation induces distinct signaling pathways in naïve vs. antigen-experienced T cells
Mark M. Davisa,c,1
aThe Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; bDepartment of Parasitology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan; and cDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
Contributed by Mark M. Davis, December 3, 2010 (sent for review May 10, 2010)
Naïve T lymphocytes display weaker and slower responsesthan antigen-experienced cells for reasons that are not wellunderstood. Here we show that T-cell receptor (TCR) stimulationinduces distinct ERK and p38 phosphorylation patterns in naïveand antigen-experienced human T cells, and that these contributeto the differential responses shown by these cells. Specifically,TCR ligation triggers the activation of the ERK pathway in naïvecells. This phosphorylation of ERK attenuates subsequent calciuminflux and accelerates the degradation of the signalsome. Incontrast, anti-CD3 stimulation of experienced cells resultsin the phosphorylation of p38 via an association with Discslarge (Dlg). Thus, there are distinct signaling pathways triggeredby TCR ligation that impair signaling in naïve cells andfacilitate it in antigen-experienced cells.
Key Words: T-cell signaling
Freely available online through the PNAS open access option.
Author contributions: K.A. and M.M.D. designed research; K.A.performed research; K.A. and M.M.D. analyzed data; and K.A.and M.M.D. wrote the paper.