The T-cell receptor--structure, function, and clinical application.

Abstract

T cells play a central role in the immune system as effectors and regulators. They become activated upon antigen recognition by their T-cell receptors (TCR). The TCR repertoire is established by developmentally regulated TCR gene rearrangements and shaped by predominantly intrathymic selection processes. Failure of this system can lead to autoimmune disease. TCR gene probes and primers are widely used to distinguish polyclonal from abnormal clonal T-cell proliferations in Southern blot or polymerase chain reaction (PCR) procedures. T cells are normally activated by signal transduction through the TCR/CD3 complex and accessory molecules such as CD4 and CD8. Protein tyrosine kinases (PTKs) and nuclear transcription factors (TFs) are important intracellular signaling molecules. Chromosomal abnormalities in T-cell leukemia often affect the gene loci of TFs, PTKs, and sometimes other growth regulatory proteins. Aberrant activation of these molecules may lead to alteration of the signaling cascade and interference with ordered T-cell development and differentiation. The increasing knowledge about different functional aspects of TCR physiology thus contributes to the diagnosis and understanding of reactive and malignant T-cell disorders. This will eventually lead to new diagnostic concepts and novel therapeutic strategies.