The T Cell Receptor as a Multicomponent Signalling Machine: CD4/CD8 Coreceptors and CD45 in T Cell Activation

The T cell receptor is a multicomponent signalling machine. The three main components are the hypervariable alpha: beta heterodimer that confers specificity and its attendant invariant chains CD3 gamma, delta, and epsilon and the zeta:zeta or zeta:eta, the CD4 or CD8 coreceptor, and CD45. Each of these components is required for efficient signal transduction, and each has relevant enzymatic activity associated with it. The invariant part of the T cell receptor is associated with the tyrosine kinase p59fyn, the coreceptors are associated with the tyrosine kinase p56lck, and the cytoplasmic domain of CD45 has tyrosine-specific phosphatase activity. Moreover, there is strong evidence that these components interact in the plane of the membrane, and that these interactions are relevant for signal transduction. Finally, changes in the structure of CD45 that occur during differentiation of T cells alter the interactions of these three components of the signal transducing machinery, perhaps accounting for changes in signal transduction that accompany T-cell development in the thymus and the development of immunological memory cells.