T-Lymphocyte Activation and Cell Signaling

Abstract

This chapter reviews signaling events associated with T-cell activation. Crystal structure analysis has confirmed that the molecular specificity of the T-cell receptor (TCR) is conferred by the solvent-exposed membrane-distal variable regions of the α and β chains. The earliest biochemical events elicited by T-cell activation are the phosphorylation of proteins in the TCR-CD3 complex and the activation and interaction of Syk and Src family protein tyrosine kinases (PTKs). Importantly, LAT is palmitoylated, which targets it (and the molecules it recruits) to glycolipid-enriched microdomains known as lipid rafts. Recruitment of the tyrosine-phosphorylated TCR to lipid rafts is a critical step in T-cell activation and presumably concentrates the downstream signaling machinery in close proximity, facilitating enzymatic activity and molecular scaffold formation. The reorientation and redistribution of the cytoskeleton constitute an important consequence of T-cell activation, since they are closely linked to functional outcome. Defects affecting the termination of T-cell activation and growth may result in systemic autoimmune disease. The sensitivity of the quantitative fluorescence is based on the use of the standard curve as described in the standardization section. The combined use of flow cytometry and evolving technologies, such as gene microarray systems and proteomics, will tremendously increase the understanding in the field of T-lymphocyte activation and signaling.