Regulatory idiotopes / Constantin A. Bona.

  • Bona, Constantin A.
Date:
[1987], ©1987
Catalogue details

Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: Regulatory idiotopes / Constantin A. Bona. Source: Wellcome Collection.

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    1.2. GENES ENCODING ANTIGEN RECEPTOR OF T CELLS 11 DT recombinant to another DT (Kavaler et al. 1984). A D segment of human T-cell receptor was also identified (Clarke et al. 1984). Alt et al. (1984) demon¬ strated that in В cells the first recombinatorial event occurs between the D and J segments. In T cells, Siu et al. (1984) have found that an early joining event re¬ sults in the production of a DJC transcript initiated by a promoter located up¬ stream of the 5' end of the D segment. This truncated transcript is predominant in clones obtained from thymus and is very rarely found in mature T lymphocytes in lymph nodes. Sequence analysis of Vß genes of thymus-derived hybridomas and helper and cytotoxic T-cell clones suggests that the number of expressed genes is rela¬ tively small. Behlke et al. (1985) estimated about 18-30 expressed Vß germ Une genes, whereas Barth et al. (1985) estimated only 20. Whereas at least 30% of Vh genes are pseudogenes (Brodeur and Riblet 1984), no pseudogenes have been reported. The pool of expressed germ line genes can be classified in seven to eight families based on homology of DNA sequence and the pattern of hybridization in Southern blots. In contrast to Vh and genes encoding for the variable region of immuno¬ globulins, little polymoфhism of genes was observed in Southern blots of liver DNA from five mouse strains digested with four restriction endonucleases. Six isolated Vh probes hybridize to a single band, two with two bands and one with three. SJL mice have deleted two Vß families (Behlke et al. 1985), whereas Cß, DJç, gene segments are deleted in NZB mice. Comparison of sequence of VTß from clones or hybridomas with various antigenic specificities and further analysis in the Wu-Kabat variability plot used to define hypervariable regions of Igs showed that Утр exhibits seven hypervar¬ iable regions. Three of them correspond to well-defined CDRs of the chain and two of them to subgroup fragments of Vh and V^; two have no precedent in the V region of Igs (Patten et al. 1984). The most striking differences when the sequences of Vß chain are compared with Vh are the lack of extended frame¬ work regions and extensive variability in either end of the D segment, where one to six added extra-nucleotides have been observed. No somatic mutations were observed in coding V, D, and J segments of ß-chains from T-cell clones with the same specificity. Therefore it appears that the major mechanisms that could be responsible for the diversity of Vß T genes result from junctional flexibility in joining V and J segments with D segment and combinatorial joining, which permits the recom¬ bination of 20-30 Vß genes with the Dß segment and six segments of two J clus¬ ters. Barth et al. (1985) consider thatDß gene segments may join to Vß segments with equal probability in all three translational reading frames. The genes