Lymphocyte Activation Signals: Transduction

B and T lymphocytes, the antigen-specific cells of the immune system, are generally quiescent and require antigen stimulation to progress from the G0 stage of the cell cycle. The immune response to pathogens or foreign substances is initiated from clonotypic receptors on these cells that recognize the antigen and induce a series of signal transduction events. These signals are fundamental in both developmental decisions and the initiation of immune responses. Antigen receptors on the lymphocytes consist of two, functional modules: a ligand-binding module and a signalling module. T and B cells possess structurally different, oligomeric receptors that recognize distinct forms of antigens. The antigen-specific receptor on T cells (T-cell receptor, TCR) is composed of clonotypic (TCRab or TCRgd) chains that are formed by deoxyribonucleic acid (DNA) recombination events during development. These clonotypic TCR chains, are noncovalently associated with the complex of invariant CD3g, d and e chains and z family dimers. The clonotypic TCRab or TCRgd chains are responsible for antigen recognition, but have a very small (five residues) cytoplasmic domain. The associated invariant CD3 and z chains have considerably larger cytoplasmic domains (40–113 residues), and are responsible for coupling to the intracellular signalling machinery. Clonotypic, antigen-recognizing receptors on B cells (BCR) are composed of membrane immunoglobulin (Ig) and are similarly expressed at the plasma membrane in a stable complex with the invariant disulfide-linked Iga and Igb molecules, which are responsible for signal transduction. Antigen recognition by the BCR or TCR produces signals leading to multiple potential outcomes: proliferation, differentiation, activation, apoptosis or anergy of the BandT-cell clones. In spite of the different receptor forms on T and B cells, the signal transduction events that result from the interaction of TCRor BCRwith antigen are quite similar. Molecules involved in the signal transduction through antigen receptors on lymphocytes are described here (summarized in Table 1). See also: B Lymphocytes: Receptors; Lymphocytes: Antigen-induced Gene Activation; Signal Transduction: Overview; T-cell Receptors; T-lymphocyte Activation