Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1996 Feb 1;183(2):439–449. doi: 10.1084/jem.183.2.439

Recurrent T cell receptor rearrangements in the cytotoxic T lymphocyte response in vivo against the p815 murine tumor

PMCID: PMC2192464  PMID: 8627157

Abstract

P815 is a murine mastocytoma of DBA/2 origin which, although immunogenic, rapidly develops as a tumor in immunocompetent syngeneic hosts. In this report, we have studied, by a molecular approach, the in vivo alpha/beta T cell response to P815. Both situations of tumor growth after engraftment of naive animals or tumor rejection by preimmunized animals have been analyzed. The spectrum of T cell receptor beta chain rearrangements in the tumor-infiltrating lymphocytes was found to be highly variable among individual tumor- bearing mice. However, two rearrangements, one using V(beta)1 and J(beta)1.2 segments and one using the V(beta)1 and J(beta)2.5 segments, with conserved junctional regions, reproducibly emerge in most individuals. These two rearrangements thus correspond to "public" (recurrent) T cell clones, as opposed to "private" ones, which emerge in a seemingly stochastic fashion in immunized animals. Importantly, these public cells are observed in situations of either growth or rejection of the tumor. Quantification provides a clear increase in public T cells in secondary responses, but no obvious correlation provides between their level and primary tumor rejection. The V(beta)1- J(beta)1.2 rearrangement is borne by CTL directed against an antigen derived from P1A, a nonmutated mouse self protein which is expressed in P815 but not in normal mouse tissues except testis. A recurrent, public T cell response can thus be observed to an antigen derived from a self protein expressed by a tumor.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

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

  1. Argaet V. P., Schmidt C. W., Burrows S. R., Silins S. L., Kurilla M. G., Doolan D. L., Suhrbier A., Moss D. J., Kieff E., Sculley T. B. Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein-Barr virus. J Exp Med. 1994 Dec 1;180(6):2335–2340. doi: 10.1084/jem.180.6.2335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boon T., Cerottini J. C., Van den Eynde B., van der Bruggen P., Van Pel A. Tumor antigens recognized by T lymphocytes. Annu Rev Immunol. 1994;12:337–365. doi: 10.1146/annurev.iy.12.040194.002005. [DOI] [PubMed] [Google Scholar]
  3. Bowness P., Moss P. A., Rowland-Jones S., Bell J. I., McMichael A. J. Conservation of T cell receptor usage by HLA B27-restricted influenza-specific cytotoxic T lymphocytes suggests a general pattern for antigen-specific major histocompatibility complex class I-restricted responses. Eur J Immunol. 1993 Jul;23(7):1417–1421. doi: 10.1002/eji.1830230702. [DOI] [PubMed] [Google Scholar]
  4. Boël P., Wildmann C., Sensi M. L., Brasseur R., Renauld J. C., Coulie P., Boon T., van der Bruggen P. BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity. 1995 Feb;2(2):167–175. doi: 10.1016/s1074-7613(95)80053-0. [DOI] [PubMed] [Google Scholar]
  5. Brichard V. G., Warnier G., Van Pel A., Morlighem G., Lucas S., Boon T. Individual differences in the orientation of the cytolytic T cell response against mouse tumor P815. Eur J Immunol. 1995 Mar;25(3):664–671. doi: 10.1002/eji.1830250306. [DOI] [PubMed] [Google Scholar]
  6. Brichard V., Van Pel A., Wölfel T., Wölfel C., De Plaen E., Lethé B., Coulie P., Boon T. The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med. 1993 Aug 1;178(2):489–495. doi: 10.1084/jem.178.2.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Casanova J. L., Maryanski J. L. Antigen-selected T-cell receptor diversity and self-nonself homology. Immunol Today. 1993 Aug;14(8):391–394. doi: 10.1016/0167-5699(93)90140-G. [DOI] [PubMed] [Google Scholar]
  8. Casanova J. L., Pannetier C., Jaulin C., Kourilsky P. Optimal conditions for directly sequencing double-stranded PCR products with sequenase. Nucleic Acids Res. 1990 Jul 11;18(13):4028–4028. doi: 10.1093/nar/18.13.4028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  10. Chothia C., Boswell D. R., Lesk A. M. The outline structure of the T-cell alpha beta receptor. EMBO J. 1988 Dec 1;7(12):3745–3755. doi: 10.1002/j.1460-2075.1988.tb03258.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cibotti R., Cabaniols J. P., Pannetier C., Delarbre C., Vergnon I., Kanellopoulos J. M., Kourilsky P. Public and private V beta T cell receptor repertoires against hen egg white lysozyme (HEL) in nontransgenic versus HEL transgenic mice. J Exp Med. 1994 Sep 1;180(3):861–872. doi: 10.1084/jem.180.3.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cochet M., Pannetier C., Regnault A., Darche S., Leclerc C., Kourilsky P. Molecular detection and in vivo analysis of the specific T cell response to a protein antigen. Eur J Immunol. 1992 Oct;22(10):2639–2647. doi: 10.1002/eji.1830221025. [DOI] [PubMed] [Google Scholar]
  13. Coulie P. G., Brichard V., Van Pel A., Wölfel T., Schneider J., Traversari C., Mattei S., De Plaen E., Lurquin C., Szikora J. P. A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med. 1994 Jul 1;180(1):35–42. doi: 10.1084/jem.180.1.35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. DUNN T. B., POTTER M. A transplantable mast-cell neoplasm in the mouse. J Natl Cancer Inst. 1957 Apr;18(4):587–601. [PubMed] [Google Scholar]
  15. 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]
  16. De Smet C., Lurquin C., van der Bruggen P., De Plaen E., Brasseur F., Boon T. Sequence and expression pattern of the human MAGE2 gene. Immunogenetics. 1994;39(2):121–129. doi: 10.1007/BF00188615. [DOI] [PubMed] [Google Scholar]
  17. Delassus S., Coutinho G. C., Saucier C., Darche S., Kourilsky P. Differential cytokine expression in maternal blood and placenta during murine gestation. J Immunol. 1994 Mar 1;152(5):2411–2420. [PubMed] [Google Scholar]
  18. Hirsch H. H., Nair A. P., Moroni C. Suppressible and nonsuppressible autocrine mast cell tumors are distinguished by insertion of an endogenous retroviral element (IAP) into the interleukin 3 gene. J Exp Med. 1993 Aug 1;178(2):403–411. doi: 10.1084/jem.178.2.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lehner P. J., Wang E. C., Moss P. A., Williams S., Platt K., Friedman S. M., Bell J. I., Borysiewicz L. K. Human HLA-A0201-restricted cytotoxic T lymphocyte recognition of influenza A is dominated by T cells bearing the V beta 17 gene segment. J Exp Med. 1995 Jan 1;181(1):79–91. doi: 10.1084/jem.181.1.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lethé B., van den Eynde B., van Pel A., Corradin G., Boon T. Mouse tumor rejection antigens P815A and P815B: two epitopes carried by a single peptide. Eur J Immunol. 1992 Sep;22(9):2283–2288. doi: 10.1002/eji.1830220916. [DOI] [PubMed] [Google Scholar]
  21. Ley V., Langlade-Demoyen P., Kourilsky P., Larsson-Sciard E. L. Interleukin 2-dependent activation of tumor-specific cytotoxic T lymphocytes in vivo. Eur J Immunol. 1991 Mar;21(3):851–854. doi: 10.1002/eji.1830210350. [DOI] [PubMed] [Google Scholar]
  22. Ley V., Roth C., Langlade-Demoyen P., Larsson-Sciard E. L., Kourilsky P. A novel approach to the induction of specific cytolytic T cells in vivo. Res Immunol. 1990 Nov-Dec;141(9):855–863. doi: 10.1016/0923-2494(90)90185-2. [DOI] [PubMed] [Google Scholar]
  23. North R. J., Dye E. S. Ly 1+2- suppressor T cells down-regulate the generation of Ly 1-2+ effector T cells during progressive growth of the P815 mastocytoma. Immunology. 1985 Jan;54(1):47–56. [PMC free article] [PubMed] [Google Scholar]
  24. Pannetier C., Cochet M., Darche S., Casrouge A., Zöller M., Kourilsky P. The sizes of the CDR3 hypervariable regions of the murine T-cell receptor beta chains vary as a function of the recombined germ-line segments. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4319–4323. doi: 10.1073/pnas.90.9.4319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pannetier C., Delassus S., Darche S., Saucier C., Kourilsky P. Quantitative titration of nucleic acids by enzymatic amplification reactions run to saturation. Nucleic Acids Res. 1993 Feb 11;21(3):577–583. doi: 10.1093/nar/21.3.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Puisieux I., Even J., Pannetier C., Jotereau F., Favrot M., Kourilsky P. Oligoclonality of tumor-infiltrating lymphocytes from human melanomas. J Immunol. 1994 Sep 15;153(6):2807–2818. [PubMed] [Google Scholar]
  27. Takei F., Levy J. G., Kilburn D. G. In vitro induction of cytotoxicity against syngeneic mastocytoma and its suppression by spleen and thymus cells from tumor-bearing mice. J Immunol. 1976 Feb;116(2):288–293. [PubMed] [Google Scholar]
  28. 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]
  29. Uyttenhove C., Maryanski J., Boon T. Escape of mouse mastocytoma P815 after nearly complete rejection is due to antigen-loss variants rather than immunosuppression. J Exp Med. 1983 Mar 1;157(3):1040–1052. doi: 10.1084/jem.157.3.1040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Van Pel A., De Plaen E., Boon T. Selection of highly transfectable variant from mouse mastocytoma P815. Somat Cell Mol Genet. 1985 Sep;11(5):467–475. doi: 10.1007/BF01534840. [DOI] [PubMed] [Google Scholar]
  31. Van den Eynde B., Lethé B., Van Pel A., De Plaen E., Boon T. The gene coding for a major tumor rejection antigen of tumor P815 is identical to the normal gene of syngeneic DBA/2 mice. J Exp Med. 1991 Jun 1;173(6):1373–1384. doi: 10.1084/jem.173.6.1373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Van den Eynde B., Mazarguil H., Lethé B., Laval F., Gairin J. E. Localization of two cytotoxic T lymphocyte epitopes and three anchoring residues on a single nonameric peptide that binds to H-2Ld and is recognized by cytotoxic T lymphocytes against mouse tumor P815. Eur J Immunol. 1994 Nov;24(11):2740–2745. doi: 10.1002/eji.1830241125. [DOI] [PubMed] [Google Scholar]
  33. Weidmann E., Elder E. M., Trucco M., Lotze M. T., Whiteside T. L. Usage of T-cell receptor V beta chain genes in fresh and cultured tumor-infiltrating lymphocytes from human melanoma. Int J Cancer. 1993 May 28;54(3):383–390. doi: 10.1002/ijc.2910540306. [DOI] [PubMed] [Google Scholar]
  34. Weidmann E., Whiteside T. L., Giorda R., Herberman R. B., Trucco M. The T-cell receptor V beta gene usage in tumor-infiltrating lymphocytes and blood of patients with hepatocellular carcinoma. Cancer Res. 1992 Nov 1;52(21):5913–5920. [PubMed] [Google Scholar]
  35. Yoshino I., Yano T., Yoshikai Y., Murata M., Sugimachi K., Kimura G., Nomoto K. Oligoclonal T lymphocytes infiltrating human lung cancer tissues. Int J Cancer. 1991 Mar 12;47(5):654–658. doi: 10.1002/ijc.2910470504. [DOI] [PubMed] [Google Scholar]
  36. van der Bruggen P., Traversari C., Chomez P., Lurquin C., De Plaen E., Van den Eynde B., Knuth A., Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991 Dec 13;254(5038):1643–1647. doi: 10.1126/science.1840703. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES