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. 1988 Nov 1;168(5):1553–1562. doi: 10.1084/jem.168.5.1553

The SJL/J T cell response to both spontaneous and transplantable syngeneic reticulum cell sarcoma is mediated predominantly by the V beta 17a+ T cell clonotype

PMCID: PMC2189109  PMID: 2460577

Abstract

Previous studies have revealed that the reticulum cell sarcoma (RCS) of SJL/J (H-2s, IE-) mice express an "IE-like" stimulatory tumor- associated antigen, the expression of which is requisite for stimulating host T cells necessary for tumor growth. Herein, we present evidence that the predominant T cells raised in the syngeneic response to both spontaneous and transplantable RCS tumors are of the V beta 17a TCR clonotype. The V beta 17a+ clonotype of T cells has been shown to interact with IE allogeneic specificities. We demonstrate that all four characterized RCS-specific T cell hybridomas stained positively for the anti-V beta 17a mAb, KJ23a. Additionally, KJ23a, when added to cocultures of the T cell hybridomas and RCS tumors, inhibited the release of IL-2 by the hybridomas. Further, KJ23a was shown to markedly inhibit the proliferation of SJL/J T cells when cocultured with either spontaneous or transplantable RCS tumor cells. When analyzed by flow cytometry, the T cell blast population raised in response to both spontaneous and transplantable RCS were greater than 80% KJ23a+. These T cells were brightly stained by the anti-CD4 mAb, Gk1.5, and, therefore, represent class II-responsive T cells. In corroboration of the in vitro data, T cells derived from mesenteric lymph nodes of RCS tumor-bearing mice had likewise undergone a similar expansion of V beta 17a+, CD4+ T cells. Together, these results indicate that KJ23a+ T cells play an important and predominant role in the response of SJL/J mice to spontaneous RCS tumors and provide further suggestive evidence that the stimulatory antigen(s) on the RCS tumor is IE or an "IE-like" molecule. Significantly, the important role V beta 17a+ T cells play in the response to RCS suggests a potential therapeutic role for KJ23a mAb in the intervention and prevention of RCS tumors in SJL/J mice.

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Selected References

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  1. Brown P. H., Thorbecke G. J. Characterization of the molecules on SJL/J lymphomas which stimulate syngeneic T cells. J Immunol. 1985 Nov;135(5):3572–3580. [PubMed] [Google Scholar]
  2. DeKruyff R. H., Brown P. H., Thorbecke G. J., Ponzio N. M. Characterization of SJL T cell clones responsive to syngeneic lymphoma (RCS): RCS-specific clones are stimulated by activated B cells. J Immunol. 1985 Nov;135(5):3581–3586. [PubMed] [Google Scholar]
  3. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  4. Ey P. L., Prowse S. J., Jenkin C. R. Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A-sepharose. Immunochemistry. 1978 Jul;15(7):429–436. doi: 10.1016/0161-5890(78)90070-6. [DOI] [PubMed] [Google Scholar]
  5. Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
  6. Jones P. P., Murphy D. B., McDevitt H. O. Variable synthesis and expression of E alpha and Ae (E beta) Ia polypeptide chains in mice of different H-2 haplotypes. Immunogenetics. 1981;12(3-4):321–337. doi: 10.1007/BF01561674. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Katz I. R., Lerman S. P., Ponzio N. M., Shreffler D. C., Thorbecke G. J. Growth of SJL/J-derived transplantable reticulum cell sarcoma as related to its ability to induce T-cell proliferation in the host. I. Dominant negative genetic influences of other parent haplotype in F1 hybrids of SJL/J mice. J Exp Med. 1980 Feb 1;151(2):347–361. doi: 10.1084/jem.151.2.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Malissen B., Shastri N., Pierres M., Hood L. Cotransfer of the Ed alpha and Ad beta genes into L cells results in the surface expression of a functional mixed-isotype Ia molecule. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3958–3962. doi: 10.1073/pnas.83.11.3958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Marrack P., Kappler J. T cells can distinguish between allogeneic major histocompatibility complex products on different cell types. Nature. 1988 Apr 28;332(6167):840–843. doi: 10.1038/332840a0. [DOI] [PubMed] [Google Scholar]
  12. Marrack P., Kappler J. The T cell receptor. Science. 1987 Nov 20;238(4830):1073–1079. doi: 10.1126/science.3317824. [DOI] [PubMed] [Google Scholar]
  13. Marshak-Rothstein A., Fink P., Gridley T., Raulet D. H., Bevan M. J., Gefter M. L. Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 locus. J Immunol. 1979 Jun;122(6):2491–2497. [PubMed] [Google Scholar]
  14. Mathis D. J., Benoist C., Williams V. E., 2nd, Kanter M., McDevitt H. O. Several mechanisms can account for defective E alpha gene expression in different mouse haplotypes. Proc Natl Acad Sci U S A. 1983 Jan;80(1):273–277. doi: 10.1073/pnas.80.1.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nakauchi H., Osada H., Yagita H., Okumura K. Molecular evidence that SJL reticulum cell sarcomas are derived from pre-B cell. Clonal rearrangement of heavy chain but not of light chain immunoglobulin genes. J Immunol. 1987 Oct 15;139(8):2803–2809. [PubMed] [Google Scholar]
  16. Ohnishi K., Bonavida B. Mapping of SJL/J reticulum cell sarcoma tumor-associated Ia antigens by T cell hybridomas: characterization of tumor-specific and shared epitopes detected on IE+ allogeneic cells. J Immunol. 1986 Jul 15;137(2):733–740. [PubMed] [Google Scholar]
  17. Ohnishi K., Bonavida B. Regulation of Ia+ reticulum cell sarcoma (RCS) growth in syngeneic SJL/J mice. I. Inhibition of tumor growth by passive administration of L3T4 monoclonal antibody before or after tumor inoculation. J Immunol. 1987 Jun 15;138(12):4524–4529. [PubMed] [Google Scholar]
  18. Sakano T., Bonavida B. Inhibition of IA positive reticulum cell sarcoma tumor cell growth in syngeneic SJL/J mice by passive administration of monoclonal anti-IA antibody. Cancer Res. 1986 Jul;46(7):3245–3248. [PubMed] [Google Scholar]
  19. Song E. S., Linsk R., Olson C. A., McMillan M., Goodenow R. S. Allospecific cytotoxic T lymphocytes recognize an H-2 peptide in the context of a murine major histocompatibility complex class I molecule. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1927–1931. doi: 10.1073/pnas.85.6.1927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Wilbur S. M., Bonavida B. Expression of hybrid Ia molecules on the cell surface of reticulum cell sarcomas that are undetectable on host SJL/J lymphocytes. J Exp Med. 1981 Mar 1;153(3):501–513. doi: 10.1084/jem.153.3.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wilbur S. M., Marelli O., Bonavida B. Serological demonstration of an allogeneic Ia.7 antigen on the cell surface of SJL/J-derived reticulum cell sarcomas. Cancer Res. 1983 Sep;43(9):4266–4270. [PubMed] [Google Scholar]

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