Co-stimulation of T cells with CD2 augments TCR-CD3-mediated activation of protein tyrosine kinase p72syk, resulting in increased tyrosine phosphorylation of adapter proteins, Shc and Cbl |
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Authors: | Umehara H; Huang JY; Kono T; Tabassam FH; Okazaki T; Gouda S; Nagano Y; Bloom ET; Domae N |
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Institution: | Department of Medicine, Osaka Dental University, Japan. |
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Abstract: | Complete T cell activation requires not only the first signal via TCR- CD3
engagement, but also a co-stimulatory signal through accessory receptors
such as CD2, LFA-1 and CD28. However, the pathway of co- stimulatory
signaling through accessory receptors is incompletely understood. We report
here that CD2 provides a co-stimulus for activation of CD3-mediated
syk/ZAP-70 family kinase, p72Syk (Syk), in Jurkat T cells. Although
cross-linking of CD2 alone or any combination of CD2 with LFA-1alpha,
LFA-1beta or CD28 did not induce tyrosine phosphorylation of Syk,
co-cross-linking of CD2 with CD3 enhanced CD3- mediated tyrosine
phosphorylation of Syk. Enhancement of tyrosine phosphorylation of Syk by
CD2 co-stimulation was CD2 antibody concentration-dependent, and time
course studies showed that CD2 co- stimulation enhanced Syk tyrosine
phosphorylation by 30 s and through 5 min stimulation compared with the
control. In vitro kinase assay revealed that co-cross-linking of CD2 with
CD3 augmented Syk kinase activity using myelin basic protein as a
substrate. Furthermore, CD2 co- stimulation with CD3 resulted in enhanced
tyrosine phosphorylation of adapter proteins, such as Shc and Cbl, in an
antibody concentration- dependent manner. Finally, CD2 provided a
co-stimulatory signals for synthesis of IL-2 in Jurkat cells and
phytohemagglutinin (PHA)- activated T cells and for proliferation of
PHA-activated T cells. Taken together, these results indicate that CD2 is
an important co- stimulatory receptor for CD3-mediated T cell activation
and functions in concert with CD3.
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