A Possible Basis for Major Histocompatibility Complex-Restricted T-Cell Recognition

• Published in: Philosophical transactions of the Royal Society of London. Series B. Biological sciences Vol. 323; no. 1217; pp. 521 - 524
• Main Authors: Davis, M M, Chien, Y H, Bjorkman, P J, Elliott, J F, Iwashima, M, Rock, E P, Patten, P A
• Format: Journal Article
• Language: English
• Published: England The Royal Society 12.06.1989
• Subjects: Antibody Diversity; Gene Rearrangement, T-Lymphocyte; Genes, Immunoglobulin; Humans; Major Histocompatibility Complex; Receptors, Antigen, T-Cell - genetics; T-Lymphocytes - immunology
• ISSN: 0962-8436; 1471-2970
• DOI: 10.1098/rstb.1989.0030

Four distinct T-cell antigen-receptor gene loci have now been identified and partly characterized: $\alpha, \beta, \gamma$ and $\delta$. All of these loci can rearrange in an immunoglobulinlike fashion and express polypeptides that contribute to either $\alpha: \beta$ or $\gamma : \delta$ T-cell receptor-CD3 complexes. Surprisingly, the T-cell receptor (TCR) $\delta$ coding regions are located entirely, or almost entirely, within the TCR a locus and share at least some of the V region gene segments, thus at least partly linking the two different types of receptor heterodimers. Analysis of potential T-cell receptor diversity, particularly that of the $\delta$ chain, indicates a striking concentration of somatic polymorphism in the V-J junctional region of the two heterodimers, four to six orders of magnitude higher than similar calculations for immunoglobulin light- and heavy-chain combinations. In contrast, the number of possible V region combinations in T-cell receptors is one hundredth to one thousandth that of immunoglobulins. TCR $\alpha: \delta$: heterodimers are known to recognize many possible fragments of antigens embedded in the peptidebinding clefts of a relatively small number of major histocompatibility complex (MHC) molecules. Thus it is attractive to speculate that the V-J junctional portions of both types of T-cell receptor contact peptide antigens, whereas the remaining diversity regions contact the MHC. This contention is supported by molecular modelling studies and has interesting implications for the evolution of antigen-receptor genes.