title: A possible basis for major histocompatibility complex-restricted T-cell recognition.
abstract: 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 immunoglobulin-like 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 alpha 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: beta heterodimers are known to recognize many possible fragments of antigens embedded in the peptide-binding 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.
authors.affiliation: Howard Hughes Medical Institute, Stanford University School of Medicine, California 94305.
authors.forename: M M
authors.initials: MM
authors.lastname: Davis
authors.forename: Y H
authors.initials: YH
authors.lastname: Chien
authors.forename: P J
authors.initials: PJ
authors.lastname: Bjorkman
authors.forename: J F
authors.initials: JF
authors.lastname: Elliott
authors.forename: M
authors.initials: M
authors.lastname: Iwashima
authors.forename: E P
authors.initials: EP
authors.lastname: Rock
authors.forename: P A
authors.initials: PA
authors.lastname: Patten
mesh_terms: D000916:Antibody Diversity; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D008285:Major Histocompatibility Complex; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell