The Human T Cell Receptor in Health and Disease

Abstract

The T cell antigen receptor (TCR) recognizes antigen in the form of short peptides bound to a major histocompatibility (MHC) molecule. This review provides a synopsis of the current state of knowledge of the structure and function of the receptor and its possible role in human disease. Analysis of the T cell receptor usage of T-cell lines and clones recognizing the same peptide-MHC complex is beginning to shed light onto the structural basis of the TCR-peptide-MHC complex. Also, it is now apparent that there are two mechanisms by which the TCR can interact with the MHC molecule, either through classical peptide interactions or through super-antigens. Finally, we review the role of specific TCRs in human disease. Current evidence in this area is difficult to interpret; however, it is likely that TCR-mediated disease susceptibility exists, and its basis at either a germline or somatic level will soon be clarified.

Structure and specificity of T cell receptors expressed by potentially pathogenic anti-DNA autoantibody-inducing T cells in human lupus.

“…Although the TCR gene usage was heterogeneous in this spontaneous and systemic autoimmune disease, there were some notable recurrences besides the charged motifs. In four of the five patients, the frequency of Va8 gene usage was markedly increased among their pathogenic autoantibody-inducing Th lines ranging from 36 to 100%, in contrast to normal peripheral blood T cells where its expression is only 9% (31,32). The frequency of Va8 gene usage was not increased in the total T cell population of lupus patients but only in these select autoimmune Th cells from four out of the five patients.…”

Genetic control of T cell receptor BJ gene expression in peripheral lymphocytes of normal and rheumatoid arthritis monozygotic twins.

“…Previous studies on the TCRBJ gene repertoires of human PBL were carried out by random sequencing of TCR cDNA (25,(34)(35)(36)(37)(38)(39) and by PCR-Southern blot hybridization (40,41). The results of these early investigations agree with our determination that BJ2 cluster genes are more commonly used than BJ1 cluster genes, that the BJ2S1 gene is used very frequently and that the BJ1S4, BJ1S6, BJ2S4, and BJ2S6 genes are used uncommonly.…”

The Universal Character of the Tumor-Associated Antigen Survivin

“…A T cell expresses a unique antigen-binding molecule called the T-cell receptor on the cell surface. In contrast to membrane-bound antibodies on B cells, which can recognize antigen alone, the vast majority of T-cell receptors recognize a complex ligand, comprising an antigenic peptide bound to MHC-derived molecules (26). The formation of peptide-MHC complexes requires that a protein antigen is degraded by a sequence of events called antigen processing.…”