The role of T-cell receptors in health and disease

The progress made in the last several years in understanding the biology of the human T-cell receptor has enabled the start of the formidable task of deciphering the mechanisms that result in the pathogenesis of several important disease states in man. The ability to clone T-cells, and to identify TCR utilization by genetic techniques, has greatly enhanced our ability to diagnose T-cell malignancy and follow its response to treatment. The phenomenon of superantigen activation of TCR has improved our understanding of certain disorders associated with infections in humans. We are now prepared to use new knowledge to begin to dissect the role of T-cells in initiating and perpetuating human autoimmune disease. However, several impediments to progress must first be overcome. One of the most problematic is our failure to identify autoantigens that are relevant to specific disease states. Experimental approaches to the analysis of TCR in humans are complicated by the high degree of genetic variability present in our outbred population. We also currently lack an accurate understanding of the structural basis of TCR/MHC interactions, and we therefore have difficulty translating the relationship of linear TCR gene sequence data to three-dimensional structure. Further progress in understanding the role of the TCR in normal human immune recognition and in disease states will be made when science is successful in bypassing these obstacles.