Abstract
We have cloned extrachromosomal circular DNAs containing T cell receptor (TCR) delta gene segments in adult mouse thymocytes and splenocytes. We find that the frequency of circular DNA clones carrying germline delta sequences is lower than that of J alpha probe-positive clones, possibly related to increasing 5' distance from the most upstream J alpha segment. This suggests that the TCR alpha/delta locus is successively rearranged from within and that the delta-containing excision products are progressively diluted out by the subsequent cell division which includes further alpha gene rearrangements. In addition, examination of delta gene excision products revealed newly identified V delta subfamilies, the reciprocal joining of two D delta elements, J delta 2 usage in thymocytes and novel sequences homologous to the human delta-gene deleting elements.
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- Allison J. P., McIntyre B. W., Bloch D. Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody. J Immunol. 1982 Nov;129(5):2293–2300. [PubMed] [Google Scholar]
- Alt F. W., Baltimore D. Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-JH fusions. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4118–4122. doi: 10.1073/pnas.79.13.4118. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Arden B., Klotz J. L., Siu G., Hood L. E. Diversity and structure of genes of the alpha family of mouse T-cell antigen receptor. 1985 Aug 29-Sep 4Nature. 316(6031):783–787. doi: 10.1038/316783a0. [DOI] [PubMed] [Google Scholar]
- Asarnow D. M., Kuziel W. A., Bonyhadi M., Tigelaar R. E., Tucker P. W., Allison J. P. Limited diversity of gamma delta antigen receptor genes of Thy-1+ dendritic epidermal cells. Cell. 1988 Dec 2;55(5):837–847. doi: 10.1016/0092-8674(88)90139-0. [DOI] [PubMed] [Google Scholar]
- Bluestone J. A., Pardoll D., Sharrow S. O., Fowlkes B. J. Characterization of murine thymocytes with CD3-associated T-cell receptor structures. Nature. 1987 Mar 5;326(6108):82–84. doi: 10.1038/326082a0. [DOI] [PubMed] [Google Scholar]
- Bonneville M., Janeway C. A., Jr, Ito K., Haser W., Ishida I., Nakanishi N., Tonegawa S. Intestinal intraepithelial lymphocytes are a distinct set of gamma delta T cells. Nature. 1988 Dec 1;336(6198):479–481. doi: 10.1038/336479a0. [DOI] [PubMed] [Google Scholar]
- Bonyhadi M., Weiss A., Tucker P. W., Tigelaar R. E., Allison J. P. Delta is the Cx-gene product in the gamma/delta antigen receptor of dendritic epidermal cells. Nature. 1987 Dec 10;330(6148):574–576. doi: 10.1038/330574a0. [DOI] [PubMed] [Google Scholar]
- Brenner M. B., McLean J., Dialynas D. P., Strominger J. L., Smith J. A., Owen F. L., Seidman J. G., Ip S., Rosen F., Krangel M. S. Identification of a putative second T-cell receptor. Nature. 1986 Jul 10;322(6075):145–149. doi: 10.1038/322145a0. [DOI] [PubMed] [Google Scholar]
- Chien Y. H., Iwashima M., Kaplan K. B., Elliott J. F., Davis M. M. A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation. 1987 Jun 25-Jul 1Nature. 327(6124):677–682. doi: 10.1038/327677a0. [DOI] [PubMed] [Google Scholar]
- Chien Y. H., Iwashima M., Wettstein D. A., Kaplan K. B., Elliott J. F., Born W., Davis M. M. T-cell receptor delta gene rearrangements in early thymocytes. Nature. 1987 Dec 24;330(6150):722–727. doi: 10.1038/330722a0. [DOI] [PubMed] [Google Scholar]
- Cron R. Q., Koning F., Maloy W. L., Pardoll D., Coligan J. E., Bluestone J. A. Peripheral murine CD3+, CD4-, CD8- T lymphocytes express novel T cell receptor gamma delta structures. J Immunol. 1988 Aug 15;141(4):1074–1082. [PubMed] [Google Scholar]
- Early P., Huang H., Davis M., Calame K., Hood L. An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell. 1980 Apr;19(4):981–992. doi: 10.1016/0092-8674(80)90089-6. [DOI] [PubMed] [Google Scholar]
- Elliott J. F., Rock E. P., Patten P. A., Davis M. M., Chien Y. H. The adult T-cell receptor delta-chain is diverse and distinct from that of fetal thymocytes. Nature. 1988 Feb 18;331(6157):627–631. doi: 10.1038/331627a0. [DOI] [PubMed] [Google Scholar]
- Fujimoto S., Tsuda T., Toda M., Yamagishi H. Transposon-like sequences in extrachromosomal circular DNA from mouse thymocytes. Proc Natl Acad Sci U S A. 1985 Apr;82(7):2072–2076. doi: 10.1073/pnas.82.7.2072. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fujimoto S., Yamagishi H. Isolation of an excision product of T-cell receptor alpha-chain gene rearrangements. Nature. 1987 May 21;327(6119):242–243. doi: 10.1038/327242a0. [DOI] [PubMed] [Google Scholar]
- Haskins K., Kubo R., White J., Pigeon M., Kappler J., Marrack P. The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody. J Exp Med. 1983 Apr 1;157(4):1149–1169. doi: 10.1084/jem.157.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hata S., Brenner M. B., Krangel M. S. Identification of putative human T cell receptor delta complementary DNA clones. Science. 1987 Oct 30;238(4827):678–682. doi: 10.1126/science.3499667. [DOI] [PubMed] [Google Scholar]
- Hayday A. C., Saito H., Gillies S. D., Kranz D. M., Tanigawa G., Eisen H. N., Tonegawa S. Structure, organization, and somatic rearrangement of T cell gamma genes. Cell. 1985 Feb;40(2):259–269. doi: 10.1016/0092-8674(85)90140-0. [DOI] [PubMed] [Google Scholar]
- Ito K., Bonneville M., Takagaki Y., Nakanishi N., Kanagawa O., Krecko E. G., Tonegawa S. Different gamma delta T-cell receptors are expressed on thymocytes at different stages of development. Proc Natl Acad Sci U S A. 1989 Jan;86(2):631–635. doi: 10.1073/pnas.86.2.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kobayashi M., Koike K. Construction and analysis of recombinant lambda phages containing mitochondrial DNA fragments. Gene. 1979 Jun;6(2):123–136. doi: 10.1016/0378-1119(79)90067-2. [DOI] [PubMed] [Google Scholar]
- Koning F., Stingl G., Yokoyama W. M., Yamada H., Maloy W. L., Tschachler E., Shevach E. M., Coligan J. E. Identification of a T3-associated gamma delta T cell receptor on Thy-1+ dendritic epidermal Cell lines. Science. 1987 May 15;236(4803):834–837. doi: 10.1126/science.2883729. [DOI] [PubMed] [Google Scholar]
- Korman A. J., Marusic-Galesic S., Spencer D., Kruisbeek A. M., Raulet D. H. Predominant variable region gene usage by gamma/delta T cell receptor-bearing cells in the adult thymus. J Exp Med. 1988 Sep 1;168(3):1021–1040. doi: 10.1084/jem.168.3.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Korman A. J., Maruyama J., Raulet D. H. Rearrangement by inversion of a T-cell receptor delta variable region gene located 3' of the delta constant region gene. Proc Natl Acad Sci U S A. 1989 Jan;86(1):267–271. doi: 10.1073/pnas.86.1.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kronenberg M., Goverman J., Haars R., Malissen M., Kraig E., Phillips L., Delovitch T., Suciu-Foca N., Hood L. Rearrangement and transcription of the beta-chain genes of the T-cell antigen receptor in different types of murine lymphocytes. Nature. 1985 Feb 21;313(6004):647–653. doi: 10.1038/313647a0. [DOI] [PubMed] [Google Scholar]
- Kunisada T., Yamagishi H., Sekiguchi T. Intracellular location of small circular DNA complexes in mammalian cell lines. Plasmid. 1983 Nov;10(3):242–250. doi: 10.1016/0147-619x(83)90038-0. [DOI] [PubMed] [Google Scholar]
- Lacy M. J., McNeil L. K., Roth M. E., Kranz D. M. T-cell receptor delta-chain diversity in peripheral lymphocytes. Proc Natl Acad Sci U S A. 1989 Feb;86(3):1023–1026. doi: 10.1073/pnas.86.3.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lew A. M., Pardoll D. M., Maloy W. L., Fowlkes B. J., Kruisbeek A., Cheng S. F., Germain R. N., Bluestone J. A., Schwartz R. H., Coligan J. E. Characterization of T cell receptor gamma chain expression in a subset of murine thymocytes. Science. 1986 Dec 12;234(4782):1401–1405. doi: 10.1126/science.3787252. [DOI] [PubMed] [Google Scholar]
- Lewis S., Gifford A., Baltimore D. DNA elements are asymmetrically joined during the site-specific recombination of kappa immunoglobulin genes. Science. 1985 May 10;228(4700):677–685. doi: 10.1126/science.3158075. [DOI] [PubMed] [Google Scholar]
- Lewis S., Gifford A., Baltimore D. Joining of V kappa to J kappa gene segments in a retroviral vector introduced into lymphoid cells. 1984 Mar 29-Apr 4Nature. 308(5958):425–428. doi: 10.1038/308425a0. [DOI] [PubMed] [Google Scholar]
- Lieber M. R., Hesse J. E., Mizuuchi K., Gellert M. Lymphoid V(D)J recombination: nucleotide insertion at signal joints as well as coding joints. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8588–8592. doi: 10.1073/pnas.85.22.8588. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Loh E. Y., Lanier L. L., Turck C. W., Littman D. R., Davis M. M., Chien Y. H., Weiss A. Identification and sequence of a fourth human T cell antigen receptor chain. Nature. 1987 Dec 10;330(6148):569–572. doi: 10.1038/330569a0. [DOI] [PubMed] [Google Scholar]
- Malissen M., McCoy C., Blanc D., Trucy J., Devaux C., Schmitt-Verhulst A. M., Fitch F., Hood L., Malissen B. Direct evidence for chromosomal inversion during T-cell receptor beta-gene rearrangements. Nature. 1986 Jan 2;319(6048):28–33. doi: 10.1038/319028a0. [DOI] [PubMed] [Google Scholar]
- Meuer S. C., Fitzgerald K. A., Hussey R. E., Hodgdon J. C., Schlossman S. F., Reinherz E. L. Clonotypic structures involved in antigen-specific human T cell function. Relationship to the T3 molecular complex. J Exp Med. 1983 Feb 1;157(2):705–719. doi: 10.1084/jem.157.2.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Brien R. L., Happ M. P., Dallas A., Palmer E., Kubo R., Born W. K. Stimulation of a major subset of lymphocytes expressing T cell receptor gamma delta by an antigen derived from Mycobacterium tuberculosis. Cell. 1989 May 19;57(4):667–674. doi: 10.1016/0092-8674(89)90135-9. [DOI] [PubMed] [Google Scholar]
- Okazaki K., Davis D. D., Sakano H. T cell receptor beta gene sequences in the circular DNA of thymocyte nuclei: direct evidence for intramolecular DNA deletion in V-D-J joining. Cell. 1987 May 22;49(4):477–485. doi: 10.1016/0092-8674(87)90450-8. [DOI] [PubMed] [Google Scholar]
- Okazaki K., Sakano H. Thymocyte circular DNA excised from T cell receptor alpha-delta gene complex. EMBO J. 1988 Jun;7(6):1669–1674. doi: 10.1002/j.1460-2075.1988.tb02994.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Owen J. J., Raff M. C. Studies on the differentiation of thymus-derived lymphocytes. J Exp Med. 1970 Dec 1;132(6):1216–1232. doi: 10.1084/jem.132.6.1216. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pardoll D. M., Fowlkes B. J., Bluestone J. A., Kruisbeek A., Maloy W. L., Coligan J. E., Schwartz R. H. Differential expression of two distinct T-cell receptors during thymocyte development. Nature. 1987 Mar 5;326(6108):79–81. doi: 10.1038/326079a0. [DOI] [PubMed] [Google Scholar]
- Rothenberg E., Lugo J. P. Differentiation and cell division in the mammalian thymus. Dev Biol. 1985 Nov;112(1):1–17. doi: 10.1016/0012-1606(85)90114-9. [DOI] [PubMed] [Google Scholar]
- 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]
- Sanger F. Determination of nucleotide sequences in DNA. Science. 1981 Dec 11;214(4526):1205–1210. doi: 10.1126/science.7302589. [DOI] [PubMed] [Google Scholar]
- Scollay R., Bartlett P., Shortman K. T cell development in the adult murine thymus: changes in the expression of the surface antigens Ly2, L3T4 and B2A2 during development from early precursor cells to emigrants. Immunol Rev. 1984 Dec;82:79–103. doi: 10.1111/j.1600-065x.1984.tb01118.x. [DOI] [PubMed] [Google Scholar]
- Scollay R. Thymus cell migration: cells migrating from thymus to peripheral lymphoid organs have a "mature" phenotype. J Immunol. 1982 Apr;128(4):1566–1570. [PubMed] [Google Scholar]
- Takagaki Y., DeCloux A., Bonneville M., Tonegawa S. Diversity of gamma delta T-cell receptors on murine intestinal intra-epithelial lymphocytes. Nature. 1989 Jun 29;339(6227):712–714. doi: 10.1038/339712a0. [DOI] [PubMed] [Google Scholar]
- Takagaki Y., Nakanishi N., Ishida I., Kanagawa O., Tonegawa S. T cell receptor-gamma and -delta genes preferentially utilized by adult thymocytes for the surface expression. J Immunol. 1989 Mar 15;142(6):2112–2121. [PubMed] [Google Scholar]
- Takeshita S., Sato M., Toba M., Masahashi W., Hashimoto-Gotoh T. High-copy-number and low-copy-number plasmid vectors for lacZ alpha-complementation and chloramphenicol- or kanamycin-resistance selection. Gene. 1987;61(1):63–74. doi: 10.1016/0378-1119(87)90365-9. [DOI] [PubMed] [Google Scholar]
- Takihara Y., Tkachuk D., Michalopoulos E., Champagne E., Reimann J., Minden M., Mak T. W. Sequence and organization of the diversity, joining, and constant region genes of the human T-cell delta-chain locus. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6097–6101. doi: 10.1073/pnas.85.16.6097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Toda M., Fujimoto S., Iwasato T., Takeshita S., Tezuka K., Ohbayashi T., Yamagishi H. Structure of extrachromosomal circular DNAs excised from T-cell antigen receptor alpha and delta-chain loci. J Mol Biol. 1988 Jul 20;202(2):219–231. doi: 10.1016/0022-2836(88)90453-6. [DOI] [PubMed] [Google Scholar]
- Toda M., Hirama T., Takeshita S., Yamagishi H. Excision products of immunoglobulin gene rearrangements. Immunol Lett. 1989 Jun 15;21(4):311–316. doi: 10.1016/0165-2478(89)90025-4. [DOI] [PubMed] [Google Scholar]
- Tsuda T., Yamagishi H., Ohnishi N., Yamada Y., Izumi H., Mori K. J. Extrachromosomal circular DNAs from murine hemopoietic tissue cells. Plasmid. 1983 Nov;10(3):235–241. doi: 10.1016/0147-619x(83)90037-9. [DOI] [PubMed] [Google Scholar]
- Weissman I. L. Thymus cell migration. J Exp Med. 1967 Aug 1;126(2):291–304. doi: 10.1084/jem.126.2.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winoto A., Baltimore D. Separate lineages of T cells expressing the alpha beta and gamma delta receptors. Nature. 1989 Mar 30;338(6214):430–432. doi: 10.1038/338430a0. [DOI] [PubMed] [Google Scholar]
- Yamagishi H., Kunisada T., Tsuda T. Small circular DNA complexes in eucaryotic cells. Plasmid. 1982 Nov;8(3):299–306. doi: 10.1016/0147-619x(82)90067-1. [DOI] [PubMed] [Google Scholar]
- Yamagishi H., Tsuda T., Fujimoto S., Toda M., Kato K., Maekawa Y., Umeno M., Anai M. Purification of small polydisperse circular DNA of eukaryotic cells by use of ATP-dependent deoxyribonuclease. Gene. 1983 Dec;26(2-3):317–321. doi: 10.1016/0378-1119(83)90205-6. [DOI] [PubMed] [Google Scholar]
- Yancopoulos G. D., Alt F. W. Developmentally controlled and tissue-specific expression of unrearranged VH gene segments. Cell. 1985 Feb;40(2):271–281. doi: 10.1016/0092-8674(85)90141-2. [DOI] [PubMed] [Google Scholar]
- Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]
- de Villartay J. P., Hockett R. D., Coran D., Korsmeyer S. J., Cohen D. I. Deletion of the human T-cell receptor delta-gene by a site-specific recombination. Nature. 1988 Sep 8;335(6186):170–174. doi: 10.1038/335170a0. [DOI] [PubMed] [Google Scholar]
- de Villartay J. P., Lewis D., Hockett R., Waldmann T. A., Korsmeyer S. J., Cohen D. I. Deletional rearrangement in the human T-cell receptor alpha-chain locus. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8608–8612. doi: 10.1073/pnas.84.23.8608. [DOI] [PMC free article] [PubMed] [Google Scholar]