Abstract
We have previously reported new Mtv loci, Mtv-48 and -51, in the Japanese laboratory mouse strains CS and NC. Here we show by backcross analysis that both Mtv-48 and -51 cosegregate with very slow deletion of T cells bearing V beta 2. The nucleotide sequences of the open reading frames in the 3' long terminal repeats of Mtv-48 and -51 were very similar to those of Mtv-DDO, mouse mammary tumor virus C4 [MMTV(C4)], and MMTV(BALB/cV), which encode V beta 2-specific superantigens. Furthermore, backcross female mice carrying Mtv-48 but not Mtv-51 were found to be able to produce milk-borne MMTV(CS), which can vigorously stimulate V beta 2-expressing T cells after local injection in vivo in an I-E-dependent manner. On the other hand, mice carrying Mtv-51 but not Mtv-48 could not produce such an MMTV in milk. The nucleotide sequences of MMTV(CS) open reading frame were completely matched with those of Mtv-48. These results indicate that the provirus Mtv-48 but not Mtv-51 is capable of producing a milk-borne virus of which the superantigen stimulates V beta 2-expressing T cells.
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- Acha-Orbea H., Palmer E. Mls--a retrovirus exploits the immune system. Immunol Today. 1991 Oct;12(10):356–361. doi: 10.1016/0167-5699(91)90066-3. [DOI] [PubMed] [Google Scholar]
- 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]
- Brandt-Carlson C., Butel J. S., Wheeler D. Phylogenetic and structural analyses of MMTV LTR ORF sequences of exogenous and endogenous origins. Virology. 1993 Mar;193(1):171–185. doi: 10.1006/viro.1993.1113. [DOI] [PubMed] [Google Scholar]
- Cho K., Ferrick D. A., Morris D. W. Structure and biological activity of the subgenomic Mtv-6 endogenous provirus. Virology. 1995 Jan 10;206(1):395–402. doi: 10.1016/s0042-6822(95)80055-7. [DOI] [PubMed] [Google Scholar]
- Choi Y., Kappler J. W., Marrack P. A superantigen encoded in the open reading frame of the 3' long terminal repeat of mouse mammary tumour virus. Nature. 1991 Mar 21;350(6315):203–207. doi: 10.1038/350203a0. [DOI] [PubMed] [Google Scholar]
- Choi Y., Marrack P., Kappler J. W. Structural analysis of a mouse mammary tumor virus superantigen. J Exp Med. 1992 Mar 1;175(3):847–852. doi: 10.1084/jem.175.3.847. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eisenberg R. A., Theofilopoulos A. N., Andrews B. S., Peters C. J., Thor L., Dixon F. J. Natural thymocytotoxic autoantibodies in autoimmune and normal mice. J Immunol. 1979 Jun;122(6):2272–2278. [PubMed] [Google Scholar]
- Ferrick D. A., Cho K., Gemmell-Hori L., Morris D. W. Genetic analysis of the effects of Mtv-2 on the T cell repertoire in the WXG-2 mouse strain. Int Immunol. 1992 Jul;4(7):805–810. doi: 10.1093/intimm/4.7.805. [DOI] [PubMed] [Google Scholar]
- Golovkina T. V., Chervonsky A., Dudley J. P., Ross S. R. Transgenic mouse mammary tumor virus superantigen expression prevents viral infection. Cell. 1992 May 15;69(4):637–645. doi: 10.1016/0092-8674(92)90227-4. [DOI] [PubMed] [Google Scholar]
- Golovkina T. V., Prescott J. A., Ross S. R. Mouse mammary tumor virus-induced tumorigenesis in sag transgenic mice: a laboratory model of natural selection. J Virol. 1993 Dec;67(12):7690–7694. doi: 10.1128/jvi.67.12.7690-7694.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Held W., Waanders G. A., Shakhov A. N., Scarpellino L., Acha-Orbea H., MacDonald H. R. Superantigen-induced immune stimulation amplifies mouse mammary tumor virus infection and allows virus transmission. Cell. 1993 Aug 13;74(3):529–540. doi: 10.1016/0092-8674(93)80054-i. [DOI] [PubMed] [Google Scholar]
- Hodes R. J., Novick M. B., Palmer L. D., Knepper J. E. Association of a V beta 2-specific superantigen with a tumorigenic milk-borne mouse mammary tumor virus. J Immunol. 1993 Feb 15;150(4):1422–1428. [PubMed] [Google Scholar]
- Itoh K., Oowada T., Mitsuoka T. Characteristic faecal flora of NC mice. Lab Anim. 1985 Jan;19(1):7–15. doi: 10.1258/002367785780890613. [DOI] [PubMed] [Google Scholar]
- Jouvin-Marche E., Marche P. N., Six A., Liebe-Gris C., Voegtle D., Cazenave P. A. Identification of an endogenous mammary tumor virus involved in the clonal deletion of V beta 2 T cells. Eur J Immunol. 1993 Nov;23(11):2758–2764. doi: 10.1002/eji.1830231106. [DOI] [PubMed] [Google Scholar]
- Kang J. J., Schwegel T., Knepper J. E. Sequence similarity between the long terminal repeat coding regions of mammary-tumorigenic BALB/cV and renal-tumorigenic C3H-K strains of mouse mammary tumor virus. Virology. 1993 Sep;196(1):303–308. doi: 10.1006/viro.1993.1480. [DOI] [PubMed] [Google Scholar]
- Kappler J. W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. doi: 10.1016/0092-8674(87)90568-x. [DOI] [PubMed] [Google Scholar]
- Kappler J. W., Staerz U., White J., Marrack P. C. Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex. Nature. 1988 Mar 3;332(6159):35–40. doi: 10.1038/332035a0. [DOI] [PubMed] [Google Scholar]
- Knight A. M., Harrison G. B., Pease R. J., Robinson P. J., Dyson P. J. Biochemical analysis of the mouse mammary tumor virus long terminal repeat product. Evidence for the molecular structure of an endogenous superantigen. Eur J Immunol. 1992 Mar;22(3):879–882. doi: 10.1002/eji.1830220339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Korman A. J., Bourgarel P., Meo T., Rieckhof G. E. The mouse mammary tumour virus long terminal repeat encodes a type II transmembrane glycoprotein. EMBO J. 1992 May;11(5):1901–1905. doi: 10.1002/j.1460-2075.1992.tb05242.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kozak C., Peters G., Pauley R., Morris V., Michalides R., Dudley J., Green M., Davisson M., Prakash O., Vaidya A. A standardized nomenclature for endogenous mouse mammary tumor viruses. J Virol. 1987 May;61(5):1651–1654. doi: 10.1128/jvi.61.5.1651-1654.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Luther S., Shakhov A. N., Xenarios I., Haga S., Imai S., Acha-Orbea H. New infectious mammary tumor virus superantigen with V beta-specificity identical to staphylococcal enterotoxin B (SEB). Eur J Immunol. 1994 Aug;24(8):1757–1764. doi: 10.1002/eji.1830240806. [DOI] [PubMed] [Google Scholar]
- Morris D. W., Young L. J., Gardner M. B., Cardiff R. D. Transfer, by selective breeding, of the pathogenic Mtv-2 endogenous provirus from the GR strain to a wild mouse line free of endogenous and exogenous mouse mammary tumor virus. J Virol. 1986 May;58(2):247–252. doi: 10.1128/jvi.58.2.247-252.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Niimi N., Wajjwalku W., Ando Y., Tomida S., Takeuchi M., Ueda M., Kaneda T., Yoshikai Y. Delay in expression of a mammary tumor provirus is responsible for defective clonal deletion during postnatal period. Eur J Immunol. 1994 Feb;24(2):488–491. doi: 10.1002/eji.1830240235. [DOI] [PubMed] [Google Scholar]
- Salmons B., Günzburg W. H. Current perspectives in the biology of mouse mammary tumour virus. Virus Res. 1987 Aug;8(2):81–102. doi: 10.1016/0168-1702(87)90022-0. [DOI] [PubMed] [Google Scholar]
- Shakhov A. N., Wang H., Acha-Orbea H., Pauley R. J., Wei W. Z. A new infectious mammary tumor virus in the milk of mice implanted with C4 hyperplastic alveolar nodules. Eur J Immunol. 1993 Nov;23(11):2765–2769. doi: 10.1002/eji.1830231107. [DOI] [PubMed] [Google Scholar]
- Staats J. Standardized nomenclature for inbred strains of mice: seventh listing for the International Committee on Standardized Genetic Nomenclature for Mice. Cancer Res. 1980 Jul;40(7):2083–2128. [PubMed] [Google Scholar]
- Tomonari K., Fairchild S., Rosenwasser O. A. Influence of viral superantigens on V beta- and V alpha-specific positive and negative selection. Immunol Rev. 1993 Feb;131:131–168. doi: 10.1111/j.1600-065x.1993.tb01534.x. [DOI] [PubMed] [Google Scholar]
- Van Nie R., Verstraeten A. A., De Moes J. Genetic transmission of mammary tumour virus by GR mice. Int J Cancer. 1977 Mar 15;19(3):383–390. doi: 10.1002/ijc.2910190316. [DOI] [PubMed] [Google Scholar]
- Wajjwalku W., Takahashi M., Miyaishi O., Lu J., Sakata K., Yokoi T., Saga S., Imai M., Matsuyama M., Hoshino M. Tissue distribution of mouse mammary tumor virus (MMTV) antigens and new endogenous MMTV loci in Japanese laboratory mouse strains. Jpn J Cancer Res. 1991 Dec;82(12):1413–1420. doi: 10.1111/j.1349-7006.1991.tb01814.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wajjwalku W., Tomida S., Takahashi M., Matsuyama M., Yoshikai Y. A gene encoding the ligand for deletion of T cells bearing TcrV beta 6 and V beta 8.1 cosegregates with a new endogenous mouse mammary tumor virus. Immunogenetics. 1993;37(5):397–400. doi: 10.1007/BF00216807. [DOI] [PubMed] [Google Scholar]
- Yazdanbakhsh K., Park C. G., Winslow G. M., Choi Y. Direct evidence for the role of COOH terminus of mouse mammary tumor virus superantigen in determining T cell receptor V beta specificity. J Exp Med. 1993 Aug 1;178(2):737–741. doi: 10.1084/jem.178.2.737. [DOI] [PMC free article] [PubMed] [Google Scholar]