The complex cellular interactions that govern the mammalian immune response are now known to include specific receptor/ligand interactions, recruitment of intracellular signaling molecules, activation of both kinases and phosphatases, and redistribution of macromolecular complexes into specific subcellular membrane locations that, in aggregate, result in transcriptional activation. While the TCR-CD3 signal is critical for activation of the resting T cell, it alone is not sufficient to initiate transcriptional activation or generate an effective immune response. A number of other coreceptor molecules, including CD4, CD8, and CD28, have now been characterized that also play important roles in initiating or amplifying the activation of the T cell. A 40 kDa member of the immunoglobulin superfamily, the CD7 molecule, has also been shown to have costimulatory activity and to induce tyrosine and lipid kinase activities. Here we will review the signaling pathways initiated by TCR, CD28, and CD7, as well as the functional consequences of signal transduction through these receptors.

Src family kinases (Lyn, Fyn, Lck, and Blk) and Syk, a tandem SH2 domain containing tyrosine kinase, have been demonstrated to be associated with the antigen receptor in B cells. Both of these categories of tyrosine kinases are presumed to be critical players in the process of antigen-mediated signal transduction. Cross-linking of membrane immunoglobulin on the surface of B cells leads to the activation of Lyn, Fyn, and Blk, which presumably associate with the cytoplasmic tails of the membrane immunoglobulin-associated Ig alpha/beta heterodimer. Receptor ligation also leads to the tyrosine phosphorylation and catalytic activation of Syk, but the mechanism of association of this kinase with the antigen receptor remains to be established. A number of phosphoproteins that can associate with the SH2 domains of Blk, Lyn, and Fyn have been described in activated B cells. We demonstrate here that Syk is one of the proteins in the lysates of activated B cells which bind to the SH2 domains of Src family kinases. Syk binds directly to the SH2 domain of Blk and complexes in vivo with Lyn and Blk in activated B cells.