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Natural and synthetic non-peptide antigens recognized by human γδ T cells

Abstract

T LYMPHOCYTES express either αβ or γδ T-cell receptor heterodimers1,2. Most αβ T cells recognize antigenic peptides bound to major histocompatibility complex molecules but the antigen recognition and biological function of γδ T cells is unknown. A major human γδ T-cell subset expressing Vγ2 and Vδ2 germline genes, but having diverse junctional sequences, is found in human mycobacterial lesions3 and responds in vitro to antigens of bacteria and parasites4–8. In addition, certain haematopoietic tumour cells are specifically recognized and lysed by these T cells9. Vγ2Vδ2-bearing T cells were shown to recognize mycobacterial antigens that are protease resistant and phosphatase sensitive10–13. Because of the difficulty in isolating natural antigens from mycobacterial culture filtrates or extracts, we synthesized a series of monoalkyl phosphates, and found that some, particularly monoethyl phosphate, could mimic the activity of mycobacterial antigens in stimulating these γδ T cells10. Here we report the identification of natural antigens produced by mycobacteria recognized by human Vγ2Vδ2-bearing T cells as isopentenyl pyrophosphate and related prenyl pyrophosphate derivatives, compounds involved in the synthesis of complex polyisoprenoid compounds in microbial and mammalian cells. Substitution of phosphate for the pyrophosphate moiety, or elimination of the double bond, greatly reduced antigenic activity of these compounds. These results provide formal evidence that, in contrast to recognition of major histocompatibility complex-bound peptide antigens by αβ T cells, human γδ T cells can recognize naturally occurring small non-peptidic antigens.

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References

  1. Marrack, P. & Kappler, J. Adv. Immun. 38, 1–30 (1986).

    Article  CAS  PubMed  Google Scholar 

  2. Porcelli, S., Brenner, B. B. & Band, H. Immun. Rev. 120, 137–183 (1991).

    Article  CAS  PubMed  Google Scholar 

  3. Modlin, R. L. et al. Nature 339, 544–548 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Kabelitz, D. et al. J. exp. Med. 171, 667–679 (1990).

    Article  CAS  PubMed  Google Scholar 

  5. Panchamoorthy, G. et al. J. Immun. 147, 3360–3369 (1991).

    CAS  PubMed  Google Scholar 

  6. De Libero, G. et al. J. exp. med. 173, 1311–1322 (1991).

    Article  CAS  PubMed  Google Scholar 

  7. Hara, T. et al. J. clin. Invest. 90, 204–210 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Goerlich, R. et al. Eur. J. Immun. 21, 2613–2616 (1991).

    Article  CAS  Google Scholar 

  9. Fisch, P. et al. Science 250, 1269–1273 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Tanaka, Y. et al. Proc. natn. Acad. Sci. U.S.A. 91, 8175–8179 (1994).

    Article  ADS  CAS  Google Scholar 

  11. Pfeffer, K. et al. Eur. J. Immun. 20, 1175–1179 (1990).

    Article  CAS  Google Scholar 

  12. Schoel, B., Sprenger, S. & Kaufmann, S. H. E. Eur. J. Immun. 24, 1886–1892 (1994).

    Article  CAS  Google Scholar 

  13. Constant, P. et al. Science 264, 267–270 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Bukowski, J. F. et al. J. Immun. 154, 998–1006 (1995).

    CAS  PubMed  Google Scholar 

  15. Khosravi, F. R., Cox, A. D., Kato, K. & Der, C. J. Cell Growth Differ. 3, 461–469 (1992).

    Google Scholar 

  16. Goldstein, J. L. & Brown, M. S. Nature 343, 425–430 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Hancock, J. F., Magee, A. I., Childs, L. E. & Marshall, C. J. Cell 57, 1167–1177 (1989).

    Article  CAS  PubMed  Google Scholar 

  18. Schafer, W. R. et al. Science 245, 379–385 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  19. Besra, G. S. et al. Proc. natn. Acad. Sci. U.S.A. 91, 12735–12739 (1994).

    Article  ADS  CAS  Google Scholar 

  20. Myant, N. B. The Biology of Cholesterol and Related Steroids 123–225 (Heinemann, London, 1981).

    Book  Google Scholar 

  21. Bukowski, J. F., Morita, C. T. & Brenner, M. B. J. Immun. 153, 5133–5140 (1994).

    CAS  PubMed  Google Scholar 

  22. Havlir, D. V., Ellner, J. J., Chervenak, K. A. & Boom, W. H. J. clin. Invest. 87, 729–733 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Beckman, E. M. et al. Nature 372, 691–694 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  24. Popják, G. et al. J. biol. Chem. 237, 56–61 (1962).

    PubMed  Google Scholar 

  25. Ames, B. N. Meth. Enzym. 8, 115–118 (1966).

    Article  CAS  Google Scholar 

  26. Eckstein, F., Bruns, W. & Parmeggiani, A. Biochemistry 23, 5225–5232 (1975).

    Article  Google Scholar 

  27. Knorre, D G., Kurbatov, V. A. & Samukov, V. V. FEBS Lett. 70, 105–108 (1976).

    Article  CAS  PubMed  Google Scholar 

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Tanaka, Y., Morita, C., Tanaka, Y. et al. Natural and synthetic non-peptide antigens recognized by human γδ T cells. Nature 375, 155–158 (1995). https://doi.org/10.1038/375155a0

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