Fyn regulates the duration of TCR engagement needed for commitment to effector function

A Filby, B Seddon, J Kleczkowska… - The Journal of …, 2007 - journals.aai.org
A Filby, B Seddon, J Kleczkowska, R Salmond, P Tomlinson, M Smida, JA Lindquist…
The Journal of Immunology, 2007journals.aai.org
In naive T cells, engagement of the TCR with agonist peptide: MHC molecules leads to
phosphorylation of key intracellular signaling intermediates within seconds and this peaks
within minutes. However, the cell does not commit to proliferation and IL-2 cytokine
production unless receptor contact is sustained for several hours. The biochemical basis for
this transition to full activation may underlie how T cells receive survival signals while
maintaining tolerance, and is currently not well understood. We show here that for CD8 T …
Abstract
In naive T cells, engagement of the TCR with agonist peptide: MHC molecules leads to phosphorylation of key intracellular signaling intermediates within seconds and this peaks within minutes. However, the cell does not commit to proliferation and IL-2 cytokine production unless receptor contact is sustained for several hours. The biochemical basis for this transition to full activation may underlie how T cells receive survival signals while maintaining tolerance, and is currently not well understood. We show here that for CD8 T cells commitment to proliferation and cytokine production requires sustained activation of the Src family kinase Lck and is opposed by the action of Fyn. Thus, in the absence of Fyn, commitment to activation occurs more rapidly, the cells produce more IL-2, and undergo more rounds of division. Our data demonstrate a role for Fyn in modulating the response to Ag in primary T cells.
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