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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Jun 1;89(11):5138–5141. doi: 10.1073/pnas.89.11.5138

Divergent viral superantigens delete V beta 5+ T lymphocytes.

K J Gollob 1, E Palmer 1
PMCID: PMC49244  PMID: 1317583

Abstract

Several murine superantigens in association with class II major histocompatibility complex proteins have been shown to cause the deletion of T cells based on the expression of particular beta-chain variable region (V beta) gene segments. We have previously shown that mice expressing the Etc-1 superantigen, encoded by an open reading frame within the 3' long terminal repeat of the endogenous mouse mammary tumor provirus (Mtv), Mtv-9, delete T cells expressing either V beta 5 or V beta 11 gene segments. Comparison of several Mtv 3' long terminal repeat open reading frame sequences has indicated that the carboxyl terminus likely encodes the V beta specificity of these proteins. Our analysis of C57BL/6 x DBA/2 recombinant inbred strains of mouse revealed three Mtv-9-negative strains that nevertheless have a low frequency of V beta 5-expressing T cells. Here we demonstrate that a second endogenous superantigen, responsible for the deletion of V beta 5-bearing T cells, is encoded by a gene mapping to Mtv-6 on chromosome 16. Surprisingly, the carboxyl-terminal sequences of the Mtv-6 and -9 superantigens are extremely divergent, in spite of the fact that they both mediate the deletion of V beta 5+ lymphocytes.

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Selected References

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  1. 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]
  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. Bill J., Kanagawa O., Linten J., Utsunomiya Y., Palmer E. Class I and class II MHC gene products differentially affect the fate of V beta 5 bearing thymocytes. J Mol Cell Immunol. 1990;4(5):269–280. [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Dialynas D. P., Wilde D. B., Marrack P., Pierres A., Wall K. A., Havran W., Otten G., Loken M. R., Pierres M., Kappler J. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. doi: 10.1111/j.1600-065x.1983.tb01083.x. [DOI] [PubMed] [Google Scholar]
  7. Dyson P. J., Knight A. M., Fairchild S., Simpson E., Tomonari K. Genes encoding ligands for deletion of V beta 11 T cells cosegregate with mammary tumour virus genomes. Nature. 1991 Feb 7;349(6309):531–532. doi: 10.1038/349531a0. [DOI] [PubMed] [Google Scholar]
  8. Frankel W. N., Rudy C., Coffin J. M., Huber B. T. Linkage of Mls genes to endogenous mammary tumour viruses of inbred mice. Nature. 1991 Feb 7;349(6309):526–528. doi: 10.1038/349526a0. [DOI] [PubMed] [Google Scholar]
  9. Happ M. P., Woodland D. L., Palmer E. A third T-cell receptor beta-chain variable region gene encodes reactivity to Mls-1a gene products. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6293–6296. doi: 10.1073/pnas.86.16.6293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. 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]
  13. 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]
  14. King L. B., Lund F. E., White D. A., Sharma S., Corley R. B. Molecular events in B lymphocyte differentiation. Inducible expression of the endogenous mouse mammary tumor proviral gene, Mtv-9. J Immunol. 1990 Apr 15;144(8):3218–3227. [PubMed] [Google Scholar]
  15. 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]
  16. MacDonald H. R., Schneider R., Lees R. K., Howe R. C., Acha-Orbea H., Festenstein H., Zinkernagel R. M., Hengartner H. T-cell receptor V beta use predicts reactivity and tolerance to Mlsa-encoded antigens. Nature. 1988 Mar 3;332(6159):40–45. doi: 10.1038/332040a0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Palmer E. Infectious origins of superantigens. Curr Biol. 1991 Apr;1(2):74–76. doi: 10.1016/0960-9822(91)90281-z. [DOI] [PubMed] [Google Scholar]
  19. Pauley R. J., Parks W. P., Popko B. J. Expression and demethylation of germinally-transmitted BALB/c mouse mammary tumor virus DNA in Abelson MuLV B-lymphoid cell lines. Virus Res. 1984;1(5):381–400. doi: 10.1016/0168-1702(84)90025-x. [DOI] [PubMed] [Google Scholar]
  20. Pullen A. M., Choi Y., Kushnir E., Kappler J., Marrack P. The open reading frames in the 3' long terminal repeats of several mouse mammary tumor virus integrants encode V beta 3-specific superantigens. J Exp Med. 1992 Jan 1;175(1):41–47. doi: 10.1084/jem.175.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pullen A. M., Marrack P., Kappler J. W. Evidence that Mls-2 antigens which delete V beta 3+ T cells are controlled by multiple genes. J Immunol. 1989 May 1;142(9):3033–3037. [PubMed] [Google Scholar]
  22. Ramsdell F., Lantz T., Fowlkes B. J. A nondeletional mechanism of thymic self tolerance. Science. 1989 Nov 24;246(4933):1038–1041. doi: 10.1126/science.2511629. [DOI] [PubMed] [Google Scholar]
  23. Roberts J. L., Sharrow S. O., Singer A. Clonal deletion and clonal anergy in the thymus induced by cellular elements with different radiation sensitivities. J Exp Med. 1990 Mar 1;171(3):935–940. doi: 10.1084/jem.171.3.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. White J., Herman A., Pullen A. M., Kubo R., Kappler J. W., Marrack P. The V beta-specific superantigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell. 1989 Jan 13;56(1):27–35. doi: 10.1016/0092-8674(89)90980-x. [DOI] [PubMed] [Google Scholar]
  25. Woodland D. L., Happ M. P., Gollob K. J., Palmer E. An endogenous retrovirus mediating deletion of alpha beta T cells? Nature. 1991 Feb 7;349(6309):529–530. doi: 10.1038/349529a0. [DOI] [PubMed] [Google Scholar]
  26. Woodland D. L., Lund F. E., Happ M. P., Blackman M. A., Palmer E., Corley R. B. Endogenous superantigen expression is controlled by mouse mammary tumor proviral loci. J Exp Med. 1991 Nov 1;174(5):1255–1258. doi: 10.1084/jem.174.5.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Woodland D., Happ M. P., Bill J., Palmer E. Requirement for cotolerogenic gene products in the clonal deletion of I-E reactive T cells. Science. 1990 Feb 23;247(4945):964–967. doi: 10.1126/science.1968289. [DOI] [PubMed] [Google Scholar]

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