Search tips
Search criteria 


Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. 1994 February; 68(2): 1165–1172.
PMCID: PMC236555

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


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

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Acha-Orbea H, Mitchell DJ, Timmermann L, Wraith DC, Tausch GS, Waldor MK, Zamvil SS, McDevitt HO, 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. [PubMed]
  • Acha-Orbea H, Shakhov AN, Scarpellino L, Kolb E, Müller V, Vessaz-Shaw A, Fuchs R, Blöchlinger K, Rollini P, Billotte J, et al. Clonal deletion of V beta 14-bearing T cells in mice transgenic for mammary tumour virus. Nature. 1991 Mar 21;350(6315):207–211. [PubMed]
  • Adkins B, Mueller C, Okada CY, Reichert RA, Weissman IL, Spangrude GJ. Early events in T-cell maturation. Annu Rev Immunol. 1987;5:325–365. [PubMed]
  • Benade LE, Ihle JN, 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. [PubMed]
  • Bill J, Kanagawa O, Woodland DL, 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. [PMC free article] [PubMed]
  • Boniver J, Declève A, Honsik C, Lieberman M, Kaplan HS. 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]
  • Davis MM, Bjorkman PJ. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Famulari NG. Murine leukemia viruses with recombinant env genes: a discussion of their role in leukemogenesis. Curr Top Microbiol Immunol. 1983;103:75–108. [PubMed]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed]
  • Gascoigne NR, Chien Y, Becker DM, Kavaler J, Davis MM. Genomic organization and sequence of T-cell receptor beta-chain constant- and joining-region genes. Nature. 1984 Aug 2;310(5976):387–391. [PubMed]
  • Grégoire C, Rebaï N, Schweisguth F, Necker A, Mazza G, Auphan N, Millward A, Schmitt-Verhulst AM, Malissen B. Engineered secreted T-cell receptor alpha beta heterodimers. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8077–8081. [PubMed]
  • Guidos CJ, Danska JS, Fathman CG, Weissman IL. 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. [PMC free article] [PubMed]
  • Guidos CJ, Weissman IL, Adkins B. Intrathymic maturation of murine T lymphocytes from CD8+ precursors. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7542–7546. [PubMed]
  • Hayward WS, Neel BG, Astrin SM. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature. 1981 Apr 9;290(5806):475–480. [PubMed]
  • Holland CA, Hartley JW, Rowe WP, 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. [PMC free article] [PubMed]
  • Hügin AW, Vacchio MS, Morse HC., 3rd A virus-encoded "superantigen" in a retrovirus-induced immunodeficiency syndrome of mice. Science. 1991 Apr 19;252(5004):424–427. [PubMed]
  • Infante AJ, Levcovitz H, Gordon V, Wall KA, Thompson PA, Krolick KA. 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]
  • 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. [PubMed]
  • Kaplan HS. On the natural history of the murine leukemias: presidential address. Cancer Res. 1967 Aug;27(8):1325–1340. [PubMed]
  • KAPLAN HS, BROWN MB, 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. [PubMed]
  • Kappler JW, 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. [PubMed]
  • Khan AS, Martin MA. 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. [PubMed]
  • Ledbetter JA, Herzenberg LA. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. [PubMed]
  • Lenz J, Celander D, Crowther RL, Patarca R, Perkins DW, Haseltine WA. Determination of the leukaemogenicity of a murine retrovirus by sequences within the long terminal repeat. Nature. 308(5958):467–470. [PubMed]
  • Lieberman M, Declève A, Ricciardi-Castagnoli P, Boniver J, Finn OJ, Kaplan HS. 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. [PubMed]
  • Lieberman M, Hansteen GA, Waller EK, Weissman IL, Sen-Majumdar A. Unexpected effects of the severe combined immunodeficiency mutation on murine lymphomagenesis. J Exp Med. 1992 Aug 1;176(2):399–405. [PMC free article] [PubMed]
  • LIEBERMAN M, KAPLAN HS. Leukemogenic activity of filtrates from radiation-induced lymphoid tumors of mice. Science. 1959 Aug 14;130(3372):387–388. [PubMed]
  • Manteuil-Brutlag S, Liu SL, Kaplan HS. Radiation leukemia virus contains two distinct viral RNAs. Cell. 1980 Mar;19(3):643–652. [PubMed]
  • Marrack P, Kushnir E, Kappler J. A maternally inherited superantigen encoded by a mammary tumour virus. Nature. 1991 Feb 7;349(6309):524–526. [PubMed]
  • McGrath MS, Weissman IL. AKR leukemogenesis: identification and biological significance of thymic lymphoma receptors for AKR retroviruses. Cell. 1979 May;17(1):65–75. [PubMed]
  • Merregaert J, Janowski M, Reddy EP. Nucleotide sequence of a radiation leukemia virus genome. Virology. 1987 May;158(1):88–102. [PubMed]
  • Möröy T, Fisher P, Guidos C, Ma A, Zimmerman K, Tesfaye A, DePinho R, Weissman I, Alt FW. IgH enhancer deregulated expression of L-myc: abnormal T lymphocyte development and T cell lymphomagenesis. EMBO J. 1990 Nov;9(11):3659–3666. [PubMed]
  • Nitta T, Oksenberg JR, Rao NA, 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. [PubMed]
  • Okada CY, Holzmann B, Guidos C, Palmer E, Weissman IL. 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]
  • O'Neill HC, McGrath MS, Allison JP, Weissman IL. 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. [PubMed]
  • Pullen AM, Marrack P, Kappler JW. The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens. Nature. 1988 Oct 27;335(6193):796–801. [PubMed]
  • Reich EP, Sherwin RS, Kanagawa O, Janeway CA., 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. [PubMed]
  • Majumdar AS, Guidos C, Kaneshima H, White JH, Marian J, Lieberman M, Weissman IL. An immunodominant murine lymphoma cell surface heterodimer marks thymic progenitor subsets. J Immunol. 1990 Jan 1;144(1):111–121. [PubMed]
  • Sen-Majumdar A, Lieberman M, Alpert S, Wiessman IL, 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. [PMC free article] [PubMed]
  • Staerz UD, Rammensee HG, Benedetto JD, Bevan MJ. 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]
  • 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]
  • Urban JL, Kumar V, Kono DH, Gomez C, Horvath SJ, Clayton J, Ando DG, Sercarz EE, 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. [PubMed]
  • 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. [PubMed]
  • Weissman IL, McGrath MS. Retrovirus lymphomagenesis: relationship of normal immune receptors to malignant cell proliferation. Curr Top Microbiol Immunol. 1982;98:103–112. [PubMed]
  • Zaller DM, 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. [PMC free article] [PubMed]
  • Zamvil SS, Mitchell DJ, Lee NE, Moore AC, Waldor MK, Sakai K, Rothbard JB, McDevitt HO, 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. [PMC free article] [PubMed]

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