Cell surface molecules and early events involved in human T lymphocyte activation

Abstract

The physiologic activation of human T cells by antigen involves events that occur between ligands and receptors at the interface of the T cell and antigen-presenting cell (or target cell). These events have been examined by identifying the cell surface receptors involved in such interactions using mAb. Whereas the T3/T cell antigen receptor plays a central role in such interactions, other T cell receptors have been identified which may also contribute to T cell activation in providing primary activation signals or by functioning as accessory molecules. Although the ligands of these other receptors are currently unknown or ill defined, it is likely that this will provide a fruitful area of investigation. The use of mAb as probes to mimic these putative ligands has facilitated the study of the requirements for activation and the biochemical events initiated by the receptors involved. The T cell receptor, a multisubunit complex, has been most intensively studied. Ligands that bind to T3/Ti cannot initiate activation by themselves and require the participation of accessory molecules. Stimulation of T3/Ti results in the formation of at least two potent intracellular second messengers, IP3 and DG, through the hydrolysis of PIP2. These second messengers, in turn, induce an increase in [Ca2+]i and the activation of pkC. These two events appear to be essential in the transcriptional activation of certain targeted genes through ill-defined pathways leading to the manifestations of T cell activation.