Antigen-Specific Signal Transduction

Lymphocytes sense and then respond to their environment utilizing a collection of membrane receptors. Arguably, the most important of these are the clonotypic antigen receptors, membrane immunoglobulin (mIg) on B cells, and T-cell receptor (TCR) on T cells. These receptors uniquely recognize specific foreign and self-antigens. In order to provide protection against pathogens, the receptor–antigen interactions in mature lymphocytes generally culminate in clonal expansion and/or differentiation into effector cells (reviewed in Nemazee et al ., 1991 ; Nossal, 1992  ; van Oers, 1999 ). On the other hand, so as to diminish the likelihood of autoimmune disease, ligation of these receptors with self-antigen in immature lymphocytes initiates a series of events leading to anergy, receptor editing, or death. While the detailed mechanisms of signal transduction in T and B cells are distinct, in many respects, the TCR and the B-cell receptor (BCR) utilize similar mechanisms ( Scheuermann and Uhr, 1995  ; van Oers, 1999 ). In particular, although neither the TCR nor the mIg possess intrinsic protein tyrosine kinase (PTK) activity, receptor-mediated protein tyrosine phosphorylation is upregulated immediately following antigen binding. Similar tyrosine kinase-dependent phosphorylation events are central to both B- and T-cell signal transduction cascades ( Chan et al., 1994 ; Gold et al ., 1990  ; Gold et al ., 1991 ). Additionally, Ca 2 + transients are evident in both cell types soon after receptor engagement of antigen so that in addition to phosphotyrosine-based signaling, signal transduction is also heavily dependent on Ca 2 + as a second messenger.