Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1994 Feb;68(2):1165–1172. doi: 10.1128/jvi.68.2.1165-1172.1994

Radiation leukemia virus-induced thymic lymphomas express a restricted repertoire of T-cell receptor V beta gene products.

A Sen-Majumdar 1, I L Weissman 1, G Hansteen 1, J Marian 1, E K Waller 1, M Lieberman 1
PMCID: PMC236555  PMID: 8289345

Abstract

We have investigated the phenotypic changes that take place during the process of neoplastic transformation in the thymocytes of C57BL/Ka mice infected by the radiation leukemia virus (RadLV). By the combined use of antibodies against the envelope glycoprotein gp70 of RadLV, the transformation-associated cell surface marker 1C11, and the CD3-T-cell receptor (TCR) complex, we found that in the RadLV-infected thymus, the earliest expression of viral gp70 is in 1C11hi cells; a small but significant percentage of these cells also express CD3. A first wave of viral replication, manifested by the expression of high levels of gp70 in thymocytes (over 70% positive), reaches a peak at 2 weeks; during this period, no significant changes are observed in the expression of 1C11 or CD3. The population of gp70+ cells is drastically reduced at 3 to 4 weeks after infection. However, a second cohort of gp70+ cells appears after 4 weeks, and these cells express high levels of 1C11 and TCR determinants as well. RadLV-induced lymphomas differ from normal thymocytes in their CD4 CD8 phenotype, with domination by one or more subsets. Characterization of TCR gene rearrangements in RadLV-induced lymphomas shows that most of these tumors are clonal or oligoclonal with respect to the J beta 2 TCR gene, while the J beta 1 TCR gene is rearranged in a minority (4 of 11) of lymphomas. TCR V beta repertoire analysis of 12 tumors reveals that 6 (50%) express exclusively the V beta 6 gene product, 2 (17%) are V beta 5+, and 1 (8%) each are V beta 8+ and V beta 9+. In normal C57BL/Ka mice, V beta 6 is expressed on 12%, V beta 5 is expressed on 9%, V beta 8 is expressed on 22%, and V beta 9 is expressed on 4% of TCRhi thymocytes. Thus, it appears that RadLV-induced thymic lymphomas are not randomly selected with respect to expressed TCR V beta type.

Full text

PDF
1169

Images in this article

Selected References

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

  1. Acha-Orbea H., Mitchell D. J., Timmermann L., Wraith D. C., Tausch G. S., Waldor M. K., Zamvil S. S., McDevitt H. O., Steinman L. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell. 1988 Jul 15;54(2):263–273. doi: 10.1016/0092-8674(88)90558-2. [DOI] [PubMed] [Google Scholar]
  2. Acha-Orbea H., Shakhov A. N., Scarpellino L., Kolb E., Müller V., Vessaz-Shaw A., Fuchs R., Blöchlinger K., Rollini P., Billotte J. Clonal deletion of V beta 14-bearing T cells in mice transgenic for mammary tumour virus. Nature. 1991 Mar 21;350(6315):207–211. doi: 10.1038/350207a0. [DOI] [PubMed] [Google Scholar]
  3. Adkins B., Mueller C., Okada C. Y., Reichert R. A., Weissman I. L., Spangrude G. J. Early events in T-cell maturation. Annu Rev Immunol. 1987;5:325–365. doi: 10.1146/annurev.iy.05.040187.001545. [DOI] [PubMed] [Google Scholar]
  4. Benade L. E., Ihle J. N., Declève A. Serological characterization of B-tropic viruses of C57BL mice: possible origin by recombination of endogenous N-tropic and xenotropic viruses. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4553–4557. doi: 10.1073/pnas.75.9.4553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bill J., Kanagawa O., Woodland D. L., Palmer E. The MHC molecule I-E is necessary but not sufficient for the clonal deletion of V beta 11-bearing T cells. J Exp Med. 1989 Apr 1;169(4):1405–1419. doi: 10.1084/jem.169.4.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Boniver J., Declève A., Honsik C., Lieberman M., Kaplan H. S. Phenotypic characterization of mice of thymus target cells susceptible to productive infection by the radiation leukemia virus. J Natl Cancer Inst. 1981 Nov;67(5):1139–1151. [PubMed] [Google Scholar]
  7. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  8. DesGroseillers L., Jolicoeur P. The tandem direct repeats within the long terminal repeat of murine leukemia viruses are the primary determinant of their leukemogenic potential. J Virol. 1984 Dec;52(3):945–952. doi: 10.1128/jvi.52.3.945-952.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Famulari N. G. Murine leukemia viruses with recombinant env genes: a discussion of their role in leukemogenesis. Curr Top Microbiol Immunol. 1983;103:75–108. doi: 10.1007/978-3-642-68943-7_4. [DOI] [PubMed] [Google Scholar]
  10. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Grégoire C., Rebaï N., Schweisguth F., Necker A., Mazza G., Auphan N., Millward A., Schmitt-Verhulst A. M., Malissen B. Engineered secreted T-cell receptor alpha beta heterodimers. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8077–8081. doi: 10.1073/pnas.88.18.8077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Guidos C. J., Danska J. S., Fathman C. G., Weissman I. L. T cell receptor-mediated negative selection of autoreactive T lymphocyte precursors occurs after commitment to the CD4 or CD8 lineages. J Exp Med. 1990 Sep 1;172(3):835–845. doi: 10.1084/jem.172.3.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Guidos C. J., Weissman I. L., Adkins B. Intrathymic maturation of murine T lymphocytes from CD8+ precursors. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7542–7546. doi: 10.1073/pnas.86.19.7542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hayward W. S., Neel B. G., Astrin S. M. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature. 1981 Apr 9;290(5806):475–480. doi: 10.1038/290475a0. [DOI] [PubMed] [Google Scholar]
  16. Holland C. A., Hartley J. W., Rowe W. P., Hopkins N. At least four viral genes contribute to the leukemogenicity of murine retrovirus MCF 247 in AKR mice. J Virol. 1985 Jan;53(1):158–165. doi: 10.1128/jvi.53.1.158-165.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hügin A. W., Vacchio M. S., Morse H. C., 3rd A virus-encoded "superantigen" in a retrovirus-induced immunodeficiency syndrome of mice. Science. 1991 Apr 19;252(5004):424–427. doi: 10.1126/science.1850169. [DOI] [PubMed] [Google Scholar]
  18. Infante A. J., Levcovitz H., Gordon V., Wall K. A., Thompson P. A., Krolick K. A. Preferential use of a T cell receptor V beta gene by acetylcholine receptor reactive T cells from myasthenia gravis-susceptible mice. J Immunol. 1992 Jun 1;148(11):3385–3390. [PubMed] [Google Scholar]
  19. KAPLAN H. S., BROWN M. B., PAULL J. Influence of bone-marrow injections on involution and neoplasia of mouse thymus after systemic irradiation. J Natl Cancer Inst. 1953 Oct;14(2):303–316. doi: 10.1093/jnci/14.2.303. [DOI] [PubMed] [Google Scholar]
  20. Kanagawa O., Palmer E., Bill J. The T cell receptor V beta 6 domain imparts reactivity to the Mls-1a antigen. Cell Immunol. 1989 Apr 1;119(2):412–426. doi: 10.1016/0008-8749(89)90255-4. [DOI] [PubMed] [Google Scholar]
  21. Kaplan H. S. On the natural history of the murine leukemias: presidential address. Cancer Res. 1967 Aug;27(8):1325–1340. [PubMed] [Google Scholar]
  22. Kappler J. W., Wade T., White J., Kushnir E., Blackman M., Bill J., Roehm N., Marrack P. A T cell receptor V beta segment that imparts reactivity to a class II major histocompatibility complex product. Cell. 1987 Apr 24;49(2):263–271. doi: 10.1016/0092-8674(87)90567-8. [DOI] [PubMed] [Google Scholar]
  23. Khan A. S., Martin M. A. Endogenous murine leukemia proviral long terminal repeats contain a unique 190-base-pair insert. Proc Natl Acad Sci U S A. 1983 May;80(9):2699–2703. doi: 10.1073/pnas.80.9.2699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. LIEBERMAN M., KAPLAN H. S. Leukemogenic activity of filtrates from radiation-induced lymphoid tumors of mice. Science. 1959 Aug 14;130(3372):387–388. doi: 10.1126/science.130.3372.387. [DOI] [PubMed] [Google Scholar]
  25. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  26. Lenz J., Celander D., Crowther R. L., Patarca R., Perkins D. W., Haseltine W. A. Determination of the leukaemogenicity of a murine retrovirus by sequences within the long terminal repeat. 1984 Mar 29-Apr 4Nature. 308(5958):467–470. doi: 10.1038/308467a0. [DOI] [PubMed] [Google Scholar]
  27. Lieberman M., Declève A., Ricciardi-Castagnoli P., Boniver J., Finn O. J., Kaplan H. S. Establishment, characterization and virus expression of cell lines derived from radiation- and virus-induced lymphomas of C57BL/Ka mice. Int J Cancer. 1979 Aug;24(2):168–177. doi: 10.1002/ijc.2910240208. [DOI] [PubMed] [Google Scholar]
  28. Lieberman M., Hansteen G. A., Waller E. K., Weissman I. L., Sen-Majumdar A. Unexpected effects of the severe combined immunodeficiency mutation on murine lymphomagenesis. J Exp Med. 1992 Aug 1;176(2):399–405. doi: 10.1084/jem.176.2.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Majumdar A. S., Guidos C., Kaneshima H., White J. H., Marian J., Lieberman M., Weissman I. L. An immunodominant murine lymphoma cell surface heterodimer marks thymic progenitor subsets. J Immunol. 1990 Jan 1;144(1):111–121. [PubMed] [Google Scholar]
  30. Manteuil-Brutlag S., Liu S. L., Kaplan H. S. Radiation leukemia virus contains two distinct viral RNAs. Cell. 1980 Mar;19(3):643–652. doi: 10.1016/s0092-8674(80)80041-9. [DOI] [PubMed] [Google Scholar]
  31. Marrack P., Kushnir E., Kappler J. A maternally inherited superantigen encoded by a mammary tumour virus. Nature. 1991 Feb 7;349(6309):524–526. doi: 10.1038/349524a0. [DOI] [PubMed] [Google Scholar]
  32. McGrath M. S., Weissman I. L. AKR leukemogenesis: identification and biological significance of thymic lymphoma receptors for AKR retroviruses. Cell. 1979 May;17(1):65–75. doi: 10.1016/0092-8674(79)90295-2. [DOI] [PubMed] [Google Scholar]
  33. Merregaert J., Janowski M., Reddy E. P. Nucleotide sequence of a radiation leukemia virus genome. Virology. 1987 May;158(1):88–102. doi: 10.1016/0042-6822(87)90241-8. [DOI] [PubMed] [Google Scholar]
  34. Möröy T., Fisher P., Guidos C., Ma A., Zimmerman K., Tesfaye A., DePinho R., Weissman I., Alt F. W. IgH enhancer deregulated expression of L-myc: abnormal T lymphocyte development and T cell lymphomagenesis. EMBO J. 1990 Nov;9(11):3659–3666. doi: 10.1002/j.1460-2075.1990.tb07577.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Nitta T., Oksenberg J. R., Rao N. A., Steinman L. Predominant expression of T cell receptor V alpha 7 in tumor-infiltrating lymphocytes of uveal melanoma. Science. 1990 Aug 10;249(4969):672–674. doi: 10.1126/science.2382141. [DOI] [PubMed] [Google Scholar]
  36. O'Neill H. C., McGrath M. S., Allison J. P., Weissman I. L. A subset of T cell receptors associated with L3T4 molecules mediates C6VL leukemia cell binding of its cognate retrovirus. Cell. 1987 Apr 10;49(1):143–151. doi: 10.1016/0092-8674(87)90764-1. [DOI] [PubMed] [Google Scholar]
  37. Okada C. Y., Holzmann B., Guidos C., Palmer E., Weissman I. L. Characterization of a rat monoclonal antibody specific for a determinant encoded by the V beta 7 gene segment. Depletion of V beta 7+ T cells in mice with Mls-1a haplotype. J Immunol. 1990 May 1;144(9):3473–3477. [PubMed] [Google Scholar]
  38. Pullen A. M., Marrack P., Kappler J. W. The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens. Nature. 1988 Oct 27;335(6193):796–801. doi: 10.1038/335796a0. [DOI] [PubMed] [Google Scholar]
  39. Reich E. P., Sherwin R. S., Kanagawa O., Janeway C. A., Jr An explanation for the protective effect of the MHC class II I-E molecule in murine diabetes. Nature. 1989 Sep 28;341(6240):326–328. doi: 10.1038/341326a0. [DOI] [PubMed] [Google Scholar]
  40. Sen-Majumdar A., Lieberman M., Alpert S., Wiessman I. L., Small M. Differentiation of CD3-4-8- thymocytes in short-term thymic stromal cell culture. J Exp Med. 1992 Aug 1;176(2):543–551. doi: 10.1084/jem.176.2.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Staerz U. D., Rammensee H. G., Benedetto J. D., Bevan M. J. Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor. J Immunol. 1985 Jun;134(6):3994–4000. [PubMed] [Google Scholar]
  42. Suzuki M., Koseki H., Mizutani Y., Kuribayashi K., Kanno M., Taniguchi M. Expansion of murine T cells bearing a unique T cell receptor beta-chain in Friend virus-induced tumor in situ. J Immunol. 1992 May 1;148(9):2968–2973. [PubMed] [Google Scholar]
  43. Urban J. L., Kumar V., Kono D. H., Gomez C., Horvath S. J., Clayton J., Ando D. G., Sercarz E. E., Hood L. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell. 1988 Aug 12;54(4):577–592. doi: 10.1016/0092-8674(88)90079-7. [DOI] [PubMed] [Google Scholar]
  44. Utsunomiya Y., Kosaka H., Kanagawa O. Differential reactivity of V beta 9 T cells to minor lymphocyte stimulating antigen in vitro and in vivo. Eur J Immunol. 1991 Apr;21(4):1007–1011. doi: 10.1002/eji.1830210422. [DOI] [PubMed] [Google Scholar]
  45. Weissman I. L., McGrath M. S. Retrovirus lymphomagenesis: relationship of normal immune receptors to malignant cell proliferation. Curr Top Microbiol Immunol. 1982;98:103–112. doi: 10.1007/978-3-642-68369-5_8. [DOI] [PubMed] [Google Scholar]
  46. Zaller D. M., Osman G., Kanagawa O., Hood L. Prevention and treatment of murine experimental allergic encephalomyelitis with T cell receptor V beta-specific antibodies. J Exp Med. 1990 Jun 1;171(6):1943–1955. doi: 10.1084/jem.171.6.1943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Zamvil S. S., Mitchell D. J., Lee N. E., Moore A. C., Waldor M. K., Sakai K., Rothbard J. B., McDevitt H. O., Steinman L., Acha-Orbea H. Predominant expression of a T cell receptor V beta gene subfamily in autoimmune encephalomyelitis. J Exp Med. 1988 May 1;167(5):1586–1596. doi: 10.1084/jem.167.5.1586. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES