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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 PLCgamma1 activation and Ca(2+) 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 PLCgamma1 activation. These results should provide a conceptual framework for understanding quantitative and qualitative aspects of CD28-mediated costimulation.


Journal article



Publication Date





935 - 945


Adaptor Proteins, Signal Transducing, Antigen-Presenting Cells, B7-1 Antigen, CD28 Antigens, CD4-Positive T-Lymphocytes, Calcium Signaling, Carrier Proteins, Cell Line, DNA-Binding Proteins, Enzyme Activation, Gene Expression Regulation, Humans, Interleukin-2, Isoenzymes, Jurkat Cells, Lymphocyte Activation, Macromolecular Substances, Membrane Proteins, NFATC Transcription Factors, Nuclear Proteins, Phosphatidylinositol 3-Kinases, Phospholipase C gamma, Phosphoproteins, Phosphorylation, Phosphotyrosine, Protein Processing, Post-Translational, Protein-Tyrosine Kinases, Receptors, Antigen, T-Cell, Recombinant Fusion Proteins, Sequence Deletion, Signal Transduction, Transcription Factors, Transfection, Type C Phospholipases, ZAP-70 Protein-Tyrosine Kinase