DNA Vaccines pp 375-395 | Cite as

Genetic Vaccination Targeting T-Cell Receptors

  • Alexis P. Godillot
  • Qiong Fang
  • Terry Higgins
  • Catherine Pachuk
  • Jean Boyer
  • David B. Weiner
  • Stuart Lessin
  • William V. Williams
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 29)

Abstract

T-cell antigen receptor (TCR) genes (which consist of variable (V), diversity (D), joining (J) and constant (C) segments) undergo rearrangement during T-cell development and result in the expression of a disulfide linked heterodimer (α and ß chains) on the surface of mature T-cells (1,2). The TCR confers specificity to each T-cell for antigen recognition (in the context of major histocompatibility (MHC) molecules (1,3). Clonal TCR-ß chain gene rearrangements have been demonstrated in DNA samples derived from cutaneous tumors, peripheral blood lymphocytes and lymph nodes of patients with cutaneous T cell lymphomas (CTCL) (4, 5, 6). Together with immunohistologic data (7), these findings indicate that CTCL is a clonal disease of malignant T cells that express α/ß-TCR.

Keywords

Phenol Lymphoma DMSO Agarose Chloroform 

References

  1. 1.
    Davis, M. M. and Bjorkman, P. J. (1988) T-cell antigen receptor genes and T-cell recognition. Nature 334, 395–402.PubMedCrossRefGoogle Scholar
  2. 2.
    Schatz, D. G., Oettinger, M. A., and Schlissel, M. S. (1992) V(D)J recombination: Molecular biology and regulation. Ann. Rev. Immunol. 10, 359–383.CrossRefGoogle Scholar
  3. 3.
    Moss, P. A. H., Rosenberg, W. M. C., and Bell, J. I. (1992) The human T cell receptor in health and disease. Ann. Rev. Immunol. 10, 71–96.CrossRefGoogle Scholar
  4. 4.
    Ralfkiaer, E. (1987) Genotypic analysis of cutaneous T-cell lymphomas. J. Invest. Dermatol. 88, 762–765.PubMedCrossRefGoogle Scholar
  5. 5.
    Weiss, L. M., Hu, E., Wood, G. S., Moulds, C., Cleary, M. L., Warnke, R., and Sklar, J. (1985) Clonal rearrangements of T-cell receptor genes in mycosis fungoides and dermatopathic lymphadenopathy. N. Engl. J. Med. 313, 539–544.PubMedCrossRefGoogle Scholar
  6. 6.
    Weiss, L. M., Wood, G. S., Hu, E., Abel, E. A., Hope, R. T., and Sklar, J. (1989) Detection of clonal T-cell receptor gene rearrangements in the peripheral blood of patients with mycosis fungoides/Sezary syndrome. J. Invest. Dermatol. 92, 601–604.PubMedCrossRefGoogle Scholar
  7. 7.
    Michie, S., Abel, E., Hoppe, R., Warnke, R., and Wood, G. S. (1989) Expression of T-cell receptor antigens in mycosis fungoides and inflammatory skin lesions. J. Invest. Dermatol. 93, 116–120.PubMedCrossRefGoogle Scholar
  8. 8.
    Lanzavecchia, A. (1993) Identifying strategies for immune intervention. Science 260, 937–944.PubMedCrossRefGoogle Scholar
  9. 9.
    Kwak, L. W., Campbell, M. J., Czerwinski, D. K., Hart, S., Miller, R. A., and Levy, R. (1992) Induction of immune responses in patients with B-cell lymphoma against the surface immunoglobulin idiotype expressed by their tumors. N. Engl. J. Med. 327, 1209–1215.PubMedCrossRefGoogle Scholar
  10. 10.
    Desquenne-Clark, L., Esch, T. R., Otvos, L., and Heber-Katz, E. (1991) T-cell receptor peptide immunization leads to enhanced and chronic experimental allergic encephalomyelitis. Proc. Natl. Acad. Sci. USA 88, 7219–7223.PubMedCrossRefGoogle Scholar
  11. 11.
    Howell, M., Winters, S., Olee, T., Powell, H., Carlo, D., and Brostoff, S. (1989) Vaccination against experimental allergic encephalomyelitis with T cell receptor peptides. Science 246, 668–670.PubMedCrossRefGoogle Scholar
  12. 12.
    Vandenbark, A., Hashim, G., and Offner, H. (1989) Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis. Nature 341, 541–544.PubMedCrossRefGoogle Scholar
  13. 13.
    Miller, R. A., Maloney, D. G., Warnke, R., and Levy, R. (1982) Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N. Engl. J. Med. 306, 517–522.PubMedCrossRefGoogle Scholar
  14. 14.
    Tao, M.-H. and Levy, R. (1993) Idiotype/granulocyte-macrophage colony-stimulating factor fusion protein as a vaccine for B-cell lymphoma. Nature 362, 755–758.PubMedCrossRefGoogle Scholar
  15. 15.
    McDonnell, W. M. and Askari, F. K. (1996) DNA vaccines. N. Engl. J. Med. 334, 42–45.PubMedCrossRefGoogle Scholar
  16. 16.
    Wang, B., Ugen, K. E., Srikantan, V., Agadjanyan, M. G., Dang, K., Sato, A. I., Refaeli, Y., Boyer, J., Williams, W. V., and Weiner, D. B. (1993) Gene inoculation generates immune responses against human immunodeficiency virus type 1. Proc. Natl. Acad. Sci. USA 90, 4156–4160.PubMedCrossRefGoogle Scholar
  17. 17.
    Pardoll, D. M. and Beckckerleg, A. M. (1995) Exposing the immunology of naked DNA vaccines. Immunity 3, 165–169.PubMedCrossRefGoogle Scholar
  18. 18.
    Waisman, A., Ruiz, P. J., Hirschberg, D. L., Gelman, A., Oksenberg, J. R., Brocke, S., Mor, F., Cohen, I. R., and Steinman, L. (1996) Suppressive vaccination with DNA encoding a variable region gene of the T-cell receptor prevents autoimmune encephalomyelitis and activates Th2 immunity. Nat. Med. 2, 899–905.PubMedCrossRefGoogle Scholar
  19. 19.
    Syrengelas, A. D., Chen, T. T., and Levy, R. (1996) DNA immunization induces protective immunity against B-cell lymphoma. Nature Genetics 2, 1038–1040.CrossRefGoogle Scholar
  20. 20.
    Rajotte, D., Haddad, P., Haman, A., Cragoe, E. J., Jr., and Hoang, T. (1992) Role of protein kinase C and the Na+/H+ antiporter in suppression of apoptosis by granulocyte macrophage colony-stimulating factor and interleukin-3. J. Biol. Chem. 267, 9980–9987.PubMedGoogle Scholar
  21. 21.
    Zwillich, S., Fang, Q., Kieber-Emmons, T., VonFeldt, J. M., Monos, D., Ramanujam, T., Wang, B., Weiner, D. B., and Williams, W. V. (1994) V alpha gene usage in rheumatoid compared with osteoarthritic synovial T cells. DNA Cell Biol. 13, 923–931.PubMedCrossRefGoogle Scholar
  22. 22.
    Williams, W. V., Kieber-Emmons, T., Fang, Q., Von Feldt, J., Wang, B., Ramanujam, T., and Weiner, D. B. (1993) Conserved motifs in rheumatoid arthritis synovial tissue T cell receptor beta chains. DNA Cell Biol. 12, 425–434.PubMedCrossRefGoogle Scholar
  23. 23.
    Williams, W. V., Fang, Q., Demarco, D., VonFeldt, J., Zurier, R. B., and Weiner, D. B. (1992) Restricted heterogeneity of T cell receptor transcripts in rheumatoid synovium. J. Clin. Invest. 90, 326–333.PubMedCrossRefGoogle Scholar
  24. 24.
    Crowe, J. S., Cooper, H. J., Smith, M. A., Sims, M. J., Parker, D., and Gewert, D. (1991) Improved cloning efficiency of polymerase chain reaction (PCR) products after proteinase K digestion. Nucleic Acids Res. 19, 184.PubMedCrossRefGoogle Scholar
  25. 25.
    Levy, D. N., Fernandes, L. S., Williams, W. V., and Weiner, D. B. (1993) Induction of cell differentiation by HIV-1 vpr. Cell 72, 541–550.PubMedCrossRefGoogle Scholar
  26. 26.
    Sambrook, J., Fritsch, E. and Maniatis, T., eds., (1989) Molecular Cloning. A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.Google Scholar
  27. 27.
    Rowen, L., Koop, B. F., and Hood, L. (1996) The complete 685-kilobase DNA sequence of the human ß T cell receptor locus. Science 272, 1755–1762.PubMedCrossRefGoogle Scholar
  28. 28.
    Kabat, E. A., ed. (1991) Sequences of proteins of immunological interest. U.S. Department of Health and Human Services, Bethesda, MD.Google Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2000

Authors and Affiliations

  • Alexis P. Godillot
    • 1
  • Qiong Fang
    • 1
  • Terry Higgins
    • 2
  • Catherine Pachuk
    • 2
  • Jean Boyer
    • 3
  • David B. Weiner
    • 3
  • Stuart Lessin
    • 4
  • William V. Williams
    • 5
  1. 1.Rheumatology Division, Department of MedicineUniversity of Pennsylvania School of MedicinePhiladelphia
  2. 2.Apollon Inc.Malvern
  3. 3.Department of Pathology and Laboratory MedicineUniversity of Pennsylvania School of MedicinePhiladelphia
  4. 4.Department of DermatologyUniversity of Pennsylvania School of Medicine and The Philadelphia Veterans Affairs Medical CenterPhiladelphia
  5. 5.Smith Kline Beecham PharmaceuticalsPhiladelphia

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