Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Reconstitution by MHC-restricted peptides of HLA-A2 heavy chain with β2-microglobulin, in vitro

Abstract

CYTOTOXIC T lymphocytes kill virally infected cells when they detect antigenic fragments presented by class I major histocompatibility complex (MHC) antigens (HLA in humans). The crystal structures of HLA-A2 and HLA-Aw68 reveal that peptide-antigen forms an integral part of the HLA structure, being retained in a prominent groove even after purification and crystallization1–3. Here we report that the heavy chain and β2-microglobulin of HLA-A2, after separation and fractionation in denaturants, reassemble efficiently under renaturing conditions only in the presence of MHC-restricted4 peptides. A complex of heavy chain, β2-microgIobulin, and viral peptide in the ratio 1:1:1 is formed in up to 46% yield. Reconstitution is not stimulated by either of two peptides not restricted to HLA-A2. The reconstituted complex of HLA-A2 and the influenza virus (B/Lee/40) nucleoprotein peptide, Np (85–94), crystallizes under conditions previously used to crystallize HLA-A2 (ref. 5). Peptide-linked folding and assembly suggests mechanisms for the unusual capacity of HLA to bind many peptides of diverse sequence.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Bjorkman, P. J. et al. Nature 329, 506–512 (1987).

    Article  CAS  ADS  Google Scholar 

  2. Bjorkman, P. J. et al. Nature 329, 512–518 (1987).

    Article  CAS  ADS  Google Scholar 

  3. Garrett, T. P. J., Saper, M. A., Bjorkman, P. J., Strominger, J. L. & Wiley, D. C. Nature 342, 692–696 (1989).

    Article  CAS  ADS  Google Scholar 

  4. Zinkernagel, R. M. & Doherty, P. C. Nature 251, 548 (1974).

    Article  ADS  Google Scholar 

  5. Bjorkman, P. J., Strominger, J. S. & Wiley, D. C. J. molec. Biol. 186, 205–210 (1985).

    Article  CAS  Google Scholar 

  6. Robbins, P. A. et al. J. Immun. 143, 4098–4103 (1989).

    CAS  PubMed  Google Scholar 

  7. Gotch, F. M., Rothbard, J., Howland, K., Townsend, A. R. M. & McMichael, A. J. Nature 326, 882 (1987).

    Article  ADS  Google Scholar 

  8. Elliot, T. J. & Eisen, H. N. Proc. natn. Acad. Sci. U.S.A. 87, 5213–5217 (1990).

    Article  ADS  Google Scholar 

  9. Chen, B. P. & Parham, P. Nature 337, 743–745 (1989).

    Article  CAS  ADS  Google Scholar 

  10. Parham, P. & Bodmer, W. F. Nature 276, 397–399 (1978).

    Article  CAS  ADS  Google Scholar 

  11. Bouillot, M. et al. Nature 339, 473–475 (1989).

    Article  CAS  ADS  Google Scholar 

  12. Frelinger, J. A., Gotch, F. M., Zweerink, H., Wain, E. & McMichael, A. J. J. exp. Med. 172, 827–834 (1990).

    Article  CAS  Google Scholar 

  13. Chen, B. P., Rothbard, J. & Parham, P. J. exp. Med. 172, 931–936 (1990).

    Article  CAS  Google Scholar 

  14. Carreno, B. M., Anderson, R. W., Coligan, J. E. & Biddison, W. E. Proc. natn. Acad. Sci. U.S.A. 87, 3420–3424 (1990).

    Article  CAS  ADS  Google Scholar 

  15. Townsend, A. et al. Nature 340, 443–448 (1989).

    Article  CAS  ADS  Google Scholar 

  16. Townsend, A. et al. Cell 62, 285–295 (1990).

    Article  CAS  Google Scholar 

  17. Kvist, S. & Hamann, U. Nature 348, 446–448 (1990).

    Article  CAS  ADS  Google Scholar 

  18. Saper, M. A., Bjorkman, P. J. & Wiley, D. C. J. molec. Biol. (in the press).

  19. Bowie, J. U., Reidhaar-Olson, J. F., Lim, W. A. & Sauer, R. T. Science 247, 1306–1310 (1990).

    Article  CAS  ADS  Google Scholar 

  20. Turner, J. J. et al. J. biol. Chem. 250, 4512–4519 (1975).

    CAS  PubMed  Google Scholar 

  21. Townsend, A. R. M. Cell 44, 959–968 (1986).

    Article  CAS  Google Scholar 

  22. Lamb, J., Eckels, D., Lake, P., Woody, J. & Green, M. Nature 300, 66–69 (1982).

    Article  CAS  ADS  Google Scholar 

  23. Carpino, L. A., Han, G. Y. & Grace Y. J. org. Chem. 37, 3404–3409 (1972).

    Article  CAS  Google Scholar 

  24. Bushkin, Y., Chorney, M. Y., Diamante, E., Fusm, S. M. & Wang, C. Y. Molec. Immun. 21, 821–829 (1984).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Silver, M., Parker, K. & Wiley, D. Reconstitution by MHC-restricted peptides of HLA-A2 heavy chain with β2-microglobulin, in vitro. Nature 350, 619–622 (1991). https://doi.org/10.1038/350619a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/350619a0

This article is cited by

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

Quick links

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