Induction of regulatory T-lymphocyte responses by liposomes carrying major histocompatibility complex molecules and foreign antigen

Abstract

Regulatory (helper and suppressor) T lymphocytes become activated only when foreign antigen is presented to them on the surface of antigen-presenting cells (APC), together with class II major histocompatibility complex (MHC) molecules (heterodimers of polypeptides of 28,000 and 35,000 relative molecular mass)1–4. Once activated by a certain foreign antigen—MHC combination, T cells react to the same antigen only in combination with the same MHC molecule, a phenomenon termed MHC restriction of T-cell recognition (reviewed in refs 1, 5). Studies of the mechanisms involved in antigen presentation and MHC restriction have been hampered mainly by the virtual impossibility of inducing T-cell responses in the absence of APC. We describe here the production of synthetic lipid vesicles with inserted class II MHC molecules and a protein antigen coupled covalently to the lipid. These liposomes are shown to stimulate cloned helper T cells and T-cell hybridomas in an antigen-specific, MHC-restricted manner in the absence of APC. Thus, the recognition of foreign antigen together with class II MHC molecules seems to be the only signal required for the activation of antigen-primed regulatory T cells. Furthermore, ‘processing’ of antigen by APC is not essential for its recognition by T cells.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Klein, J. & Nagy, Z. A. Adv. Cancer Res. 37, 233–317 (1982).

    CAS  Article  Google Scholar 

  2. 2

    Möller, G. (ed.) Immun. Rev. 35 (1977).

  3. 3

    Möller, G. (ed.) Immun. Rev. 42 (1978).

  4. 4

    Nagy, Z. A., Baxevanis, C. N., Ishii, N. & Klein, J. Immun. Rev. 60, 59–83 (1981).

    CAS  Article  Google Scholar 

  5. 5

    Zinkernagel, R. M. & Doherty, P. C. Adv. Immun. 27, 51–177 (1979).

    CAS  Article  Google Scholar 

  6. 6

    Turkewitz, A. P., Sullivan, C. P. & Mescher, M. F. Molec. Immun. 20, 1139–1147 (1983).

    CAS  Article  Google Scholar 

  7. 7

    Mimms, L. T., Zampighi, G., Nozaki, Y., Tanford, C. & Reynolds, J. A. Biochemistry 20, 833–840 (1981).

    CAS  Article  Google Scholar 

  8. 8

    Popot, J.-L., Cartaud, J. & Changeux, J.-P. Eur. J. Biochem. 118, 203–241 (1981).

    CAS  Article  Google Scholar 

  9. 9

    Barbet, J., Machy, P. & Leserman, L. D. J. Supramolec. Struct. cell. Biochem. 16, 243–258 (1981).

    CAS  Article  Google Scholar 

  10. 10

    Carlsson, J., Drevin, H. & Axen, R. Biochem. J. 173, 723–737 (1978).

    CAS  Article  Google Scholar 

  11. 11

    Engelhard, V. H., Strominger, J. L., Mescher, M. & Burakoff, S. Proc. natn. Acad. Sci. U.S.A. 75, 5688–5691 (1978).

    ADS  CAS  Article  Google Scholar 

  12. 12

    Finberg, R., Mescher, M. & Burakoff, S. J. J. exp. Med. 148, 1620–1627 (1978).

    CAS  Article  Google Scholar 

  13. 13

    Hale, A. H., Lyles, D. S. & Fan, D. P. J. Immun. 124, 724–731 (1980).

    CAS  PubMed  Google Scholar 

  14. 14

    Koszinowski, U. & Gething, M.-J. Eur. J. Immun. 10, 30–35 (1980).

    CAS  Article  Google Scholar 

  15. 15

    Weinberger, O., Herrmann, S. H., Mescher, M. F., Benacerraf, B. & Burakoff, S. J. Proc. natn. Acad. Sci. U.S.A. 77, 6091–6095 (1980).

    ADS  CAS  Article  Google Scholar 

  16. 16

    Herrmann, S. H. & Mescher, M. F. Proc. natn. Acad. Sci. U.S.A. 78, 2488–2492 (1981).

    ADS  CAS  Article  Google Scholar 

  17. 17

    Cartwright, G. S. et al. Proc. natn. Acad. Sci. U.S.A. 79, 1506–1510 (1982).

    ADS  CAS  Article  Google Scholar 

  18. 18

    Curman, B. & Östberg, L. & Peterson, P. A. Nature 272, 545–547 (1978).

    ADS  CAS  Article  Google Scholar 

  19. 19

    Malissen, B. et al. Cell 36, 319–327 (1984).

    CAS  Article  Google Scholar 

  20. 20

    Grey, H. M., Colon, S. M. & Chesnut, R. W. J. Immun. 129, 2389–2395 (1982).

    CAS  PubMed  Google Scholar 

  21. 21

    Ziegler, H. K. & Unanue, E. J. Immun. 127, 1869–1875 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Shimonkevitz, R., Kappler, J., Marrack, P. & Grey, H. J. exp. Med. 158, 303–316 (1983).

    CAS  Article  Google Scholar 

  23. 23

    Allen, P. M. & Unanue, E. R. J. Immun. 132, 1077–1079 (1984).

    CAS  Google Scholar 

  24. 24

    Benacerraf, B. J. Immun. 120, 1809–1812 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    Chesnut, R. W., Endres, R. O. & Grey, H. M. Clin. Immun. Immunopath. 15, 397–408 (1980).

    CAS  Article  Google Scholar 

  26. 26

    Baxevanis, C. N., Wernet, D., Nagy, Z. A., Maurer, P. H. & Klein, J. Immungoenetics 11, 617–628 (1980).

    CAS  Article  Google Scholar 

  27. 27

    Gillis, S. & Smith, K. A. Nature 268, 154–156 (1977).

    ADS  CAS  Article  Google Scholar 

  28. 28

    Zumbuehl, O. & Weder, H. G. Biochim. biophys. Acta 640, 252–262 (1981).

    CAS  Article  Google Scholar 

  29. 29

    Lemke, H., Hämmerling, G. J. & Hämmerling, U. Immun. Rev. 47, 175–206 (1979).

    CAS  Article  Google Scholar 

  30. 30

    Oi, V. T., Jones, P. P., Goding, J. W., Herzenberg, L. A. & Herzenberg, L. A. Curr. Topics Microbiol. Immun. 81, 115–129 (1978).

    CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Waiden, P., Nagy, Z. & Klein, J. Induction of regulatory T-lymphocyte responses by liposomes carrying major histocompatibility complex molecules and foreign antigen. Nature 315, 327–329 (1985). https://doi.org/10.1038/315327a0

Download citation

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing