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. 1985 Nov;82(22):7701–7705. doi: 10.1073/pnas.82.22.7701

Low frequency of somatic mutation in beta-chain variable region genes of human T-cell receptors.

K Ikuta, T Ogura, A Shimizu, T Honjo
PMCID: PMC391401  PMID: 3865189

Abstract

We have cloned three pairs of rearranged and germ-line variable region (V beta) genes of the beta chain of the human T-cell receptor from the cell lines ATL2, ATL12, and MT-1 of patients with adult T-cell leukemia (ATL). The pairs were derived from the same (for ATL2 and ATL12) and different (for MT-1) individuals. Comparison of the nucleotide sequences showed no somatic mutation in V beta X ATL2 and beta X ATL12-2. Although one nucleotide change was found in V beta X MT1-1, the possibility of polymorphism was not excluded. These results indicate that the frequency of somatic mutation in the V beta gene of the T-cell receptor is 1/10th or less than that in the immunoglobulin gene. Both alleles of the rearranged T-cell receptor gene were analyzed for ATL12 and MT-1. In both, only one of the two rearranged J beta alleles was an active variable-diversity-joining (V-D-J) complex. The results suggest that allelic exclusion occurs in the T-cell receptor gene.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Acuto O., Hussey R. E., Fitzgerald K. A., Protentis J. P., Meuer S. C., Schlossman S. F., Reinherz E. L. The human T cell receptor: appearance in ontogeny and biochemical relationship of alpha and beta subunits on IL-2 dependent clones and T cell tumors. Cell. 1983 Oct;34(3):717–726. doi: 10.1016/0092-8674(83)90528-7. [DOI] [PubMed] [Google Scholar]
  2. Augustin A. A., Sim G. K. T-cell receptors generated via mutations are specific for various major histocompatibility antigens. Cell. 1984 Nov;39(1):5–12. doi: 10.1016/0092-8674(84)90186-7. [DOI] [PubMed] [Google Scholar]
  3. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  4. Bernard O., Hozumi N., Tonegawa S. Sequences of mouse immunoglobulin light chain genes before and after somatic changes. Cell. 1978 Dec;15(4):1133–1144. doi: 10.1016/0092-8674(78)90041-7. [DOI] [PubMed] [Google Scholar]
  5. Bothwell A. L., Paskind M., Reth M., Imanishi-Kari T., Rajewsky K., Baltimore D. Heavy chain variable region contribution to the NPb family of antibodies: somatic mutation evident in a gamma 2a variable region. Cell. 1981 Jun;24(3):625–637. doi: 10.1016/0092-8674(81)90089-1. [DOI] [PubMed] [Google Scholar]
  6. Bothwell A. L., Paskind M., Reth M., Imanishi-Kari T., Rajewsky K., Baltimore D. Somatic variants of murine immunoglobulin lambda light chains. Nature. 1982 Jul 22;298(5872):380–382. doi: 10.1038/298380a0. [DOI] [PubMed] [Google Scholar]
  7. Chien Y. H., Gascoigne N. R., Kavaler J., Lee N. E., Davis M. M. Somatic recombination in a murine T-cell receptor gene. Nature. 1984 May 24;309(5966):322–326. doi: 10.1038/309322a0. [DOI] [PubMed] [Google Scholar]
  8. Coleclough C., Cooper D., Perry R. P. Rearrangement of immunoglobulin heavy chain genes during B-lymphocyte development as revealed by studies of mouse plasmacytoma cells. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1422–1426. doi: 10.1073/pnas.77.3.1422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Crews S., Griffin J., Huang H., Calame K., Hood L. A single VH gene segment encodes the immune response to phosphorylcholine: somatic mutation is correlated with the class of the antibody. Cell. 1981 Jul;25(1):59–66. doi: 10.1016/0092-8674(81)90231-2. [DOI] [PubMed] [Google Scholar]
  10. Gascoigne N. R., Chien Y., Becker D. M., Kavaler J., Davis M. M. Genomic organization and sequence of T-cell receptor beta-chain constant- and joining-region genes. Nature. 1984 Aug 2;310(5976):387–391. doi: 10.1038/310387a0. [DOI] [PubMed] [Google Scholar]
  11. Gershenfeld H. K., Tsukamoto A., Weissman I. L., Joho R. Somatic diversification is required to generate the V kappa genes of MOPC 511 and MOPC 167 myeloma proteins. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7674–7678. doi: 10.1073/pnas.78.12.7674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goverman J., Minard K., Shastri N., Hunkapiller T., Hansburg D., Sercarz E., Hood L. Rearranged beta T cell receptor genes in a helper T cell clone specific for lysozyme: no correlation between V beta and MHC restriction. Cell. 1985 Apr;40(4):859–867. doi: 10.1016/0092-8674(85)90345-9. [DOI] [PubMed] [Google Scholar]
  13. Hahn B., Gallo R. C., Franchini G., Popovic M., Aoki T., Salahuddin S. Z., Markham P. D., Staal F. W. Clonal selection of human T-cell leukemia virus-infected cells in vivo and in vitro. Mol Biol Med. 1984 Feb;2(1):29–36. [PubMed] [Google Scholar]
  14. Hedrick S. M., Cohen D. I., Nielsen E. A., Davis M. M. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature. 1984 Mar 8;308(5955):149–153. doi: 10.1038/308149a0. [DOI] [PubMed] [Google Scholar]
  15. Honjo T., Habu S. Origin of immune diversity: genetic variation and selection. Annu Rev Biochem. 1985;54:803–830. doi: 10.1146/annurev.bi.54.070185.004103. [DOI] [PubMed] [Google Scholar]
  16. Honjo T., Obata M., Yamawaki-Katoaka Y., Kataoka T., Kawakami T., Takahashi N., Mano Y. Cloning and complete nucleotide sequence of mouse immunoglobulin gamma 1 chain gene. Cell. 1979 Oct;18(2):559–568. doi: 10.1016/0092-8674(79)90072-2. [DOI] [PubMed] [Google Scholar]
  17. Kappler J., Kubo R., Haskins K., White J., Marrack P. The mouse T cell receptor: comparison of MHC-restricted receptors on two T cell hybridomas. Cell. 1983 Oct;34(3):727–737. doi: 10.1016/0092-8674(83)90529-9. [DOI] [PubMed] [Google Scholar]
  18. Malissen M., Minard K., Mjolsness S., Kronenberg M., Goverman J., Hunkapiller T., Prystowsky M. B., Yoshikai Y., Fitch F., Mak T. W. Mouse T cell antigen receptor: structure and organization of constant and joining gene segments encoding the beta polypeptide. Cell. 1984 Jul;37(3):1101–1110. doi: 10.1016/0092-8674(84)90444-6. [DOI] [PubMed] [Google Scholar]
  19. McIntyre B. W., Allison J. P. The mouse T cell receptor: structural heterogeneity of molecules of normal T cells defined by xenoantiserum. Cell. 1983 Oct;34(3):739–746. doi: 10.1016/0092-8674(83)90530-5. [DOI] [PubMed] [Google Scholar]
  20. Messing J., Vieira J. A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments. Gene. 1982 Oct;19(3):269–276. doi: 10.1016/0378-1119(82)90016-6. [DOI] [PubMed] [Google Scholar]
  21. Miyoshi I., Kubonishi I., Sumida M., Hiraki S., Tsubota T., Kimura I., Miyamoto K., Sato J. A novel T-cell line derived from adult T-cell leukemia. Gan. 1980 Feb;71(1):155–156. [PubMed] [Google Scholar]
  22. Morikawa S., Tatsumi E., Baba M., Harada T., Yasuhira K. Two E-rosette-forming lymphoid cell lines. Int J Cancer. 1978 Feb 15;21(2):166–170. doi: 10.1002/ijc.2910210207. [DOI] [PubMed] [Google Scholar]
  23. Patten P., Yokota T., Rothbard J., Chien Y., Arai K., Davis M. M. Structure, expression and divergence of T-cell receptor beta-chain variable regions. Nature. 1984 Nov 1;312(5989):40–46. doi: 10.1038/312040a0. [DOI] [PubMed] [Google Scholar]
  24. Pech M., Höchtl J., Schnell H., Zachau H. G. Differences between germ-line and rearranged immunoglobulin V kappa coding sequences suggest a localized mutation mechanism. Nature. 1981 Jun 25;291(5817):668–670. doi: 10.1038/291668a0. [DOI] [PubMed] [Google Scholar]
  25. Sakano H., Maki R., Kurosawa Y., Roeder W., Tonegawa S. Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes. Nature. 1980 Aug 14;286(5774):676–683. doi: 10.1038/286676a0. [DOI] [PubMed] [Google Scholar]
  26. Seidman J. G., Max E. E., Leder P. A kappa-immunoglobulin gene is formed by site-specific recombination without further somatic mutation. Nature. 1979 Aug 2;280(5721):370–375. doi: 10.1038/280370a0. [DOI] [PubMed] [Google Scholar]
  27. Siu G., Clark S. P., Yoshikai Y., Malissen M., Yanagi Y., Strauss E., Mak T. W., Hood L. The human T cell antigen receptor is encoded by variable, diversity, and joining gene segments that rearrange to generate a complete V gene. Cell. 1984 Jun;37(2):393–401. doi: 10.1016/0092-8674(84)90369-6. [DOI] [PubMed] [Google Scholar]
  28. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  29. Steinmetz M., Zachau H. G., Mach B. Cloning of immunoglobulin kappa light chain genes from mouse liver and myeloma MOPC 173. Nucleic Acids Res. 1979 Jul 25;6(10):3213–3229. doi: 10.1093/nar/6.10.3213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yanagi Y., Yoshikai Y., Leggett K., Clark S. P., Aleksander I., Mak T. W. A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature. 1984 Mar 8;308(5955):145–149. doi: 10.1038/308145a0. [DOI] [PubMed] [Google Scholar]
  31. Yoshikai Y., Anatoniou D., Clark S. P., Yanagi Y., Sangster R., Van den Elsen P., Terhorst C., Mak T. W. Sequence and expression of transcripts of the human T-cell receptor beta-chain genes. Nature. 1984 Dec 6;312(5994):521–524. doi: 10.1038/312521a0. [DOI] [PubMed] [Google Scholar]

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