TY - JOUR
T1 - CD28 as a molecular amplifier extending TCR ligation and signaling capabilities
AU - Michel, Frédérique
AU - Attal-Bonnefoy, Géraldine
AU - Mangino, Giorgio
AU - Mise-Omata, Setsuko
AU - Acuto, Oreste
N1 - Funding Information:
We would like to thank A. Alcover, D. Cantrell, D. Olive, J.M. Rojo, L. Samelson, and W. Ellmeier for reagents, plasmids, and cell lines and A. Valenzuela, F. Blanchet, R. Zaru, and S. Valitutti for help with some experiments. We thank V. Di Bartolo, D. Olive, and S. Pellegrini for critical reading of the manuscript. G.M. and S.M.-O. were recipients of the Foundation A. Cesalpino and Association pour la Recherche sur le Cancer fellowships, respectively. This work was supported by grants from the Institut Pasteur, the Association pour la Recherche sur le Cancer, and the Centre National pour la Recherche Scientifique.
PY - 2001
Y1 - 2001
N2 - Evidence has gathered that CD28 costimulation facilitates T cell activation by potentiating TCR intrinsic-signaling. However, the underlying molecular mechanism is largely unknown. Here we show that, by enhancing T cell/APC close contacts, CD28 facilitates TCR signal transduction. Moreover, the signal supplied by CD28 does not lead to increased Zap-70 and Lat phosphorylation, but amplifies PLCγ1 activation and Ca2+ response. We provide evidence that the PTK Itk controls the latter function. Our data suggest that CD28 binding to B7 contributes to setting the level of TCR-induced phosphorylated Lat for recruiting signaling complexes, whereas the CD28 signal boosts multiple pathways by facilitating PLCγ1 activation. These results should provide a conceptual framework for understanding quantitative and qualitative aspects of CD28-mediated costimulation.
AB - Evidence has gathered that CD28 costimulation facilitates T cell activation by potentiating TCR intrinsic-signaling. However, the underlying molecular mechanism is largely unknown. Here we show that, by enhancing T cell/APC close contacts, CD28 facilitates TCR signal transduction. Moreover, the signal supplied by CD28 does not lead to increased Zap-70 and Lat phosphorylation, but amplifies PLCγ1 activation and Ca2+ response. We provide evidence that the PTK Itk controls the latter function. Our data suggest that CD28 binding to B7 contributes to setting the level of TCR-induced phosphorylated Lat for recruiting signaling complexes, whereas the CD28 signal boosts multiple pathways by facilitating PLCγ1 activation. These results should provide a conceptual framework for understanding quantitative and qualitative aspects of CD28-mediated costimulation.
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U2 - 10.1016/S1074-7613(01)00244-8
DO - 10.1016/S1074-7613(01)00244-8
M3 - Article
C2 - 11754815
AN - SCOPUS:0035693742
SN - 1074-7613
VL - 15
SP - 935
EP - 945
JO - Immunity
JF - Immunity
IS - 6
ER -
