Skip to main content
SpringerLink
Log in

Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1

  • Article
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

The three-dimensional structure of the class II histocompatibility glycoprotein HLA-DR1 from human B-cell membranes has been determined by X-ray crystallography and is similar to that of class I HLA. Peptides are bound in an extended conformation that projects from both ends of an 'open-ended' antigen-binding groove. A prominent non-polar pocket into which an 'anchoring' peptide side chain fits is near one end of the binding groove. A dimer of the class II αβ heterodimers is seen in the crystal forms of HLA-DR1, suggesting class II HLA dimerization as a mechanism for initiating the cytoplasmic signalling events in T-cell activation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Rudensky, A. Y., Preston-Hurlburt, P., Hong, S.-C., Barlow, A. & Janeway, C. A. Jr Nature 353, 622–626 (1991).

    Article  CAS  ADS  Google Scholar 

  2. Hunt, D. F. et al. Science 256, 1817–1820 (1992).

    Article  CAS  ADS  Google Scholar 

  3. Chicz, R. M. et al. J. exp. Med. 178, 27–47 (1993).

    Article  CAS  Google Scholar 

  4. Chicz, R. M. et al. Nature 358, 764–768 (1992).

    Article  CAS  ADS  Google Scholar 

  5. Kappes, D. & Strominger, J. L. A. Rev. Biochem. 57, 991–1028 (1988).

    Article  CAS  Google Scholar 

  6. Tiwari, J. L. & Terasaki, P. I. HLA and Disease Associations (Springer, New York, 1985).

    Book  Google Scholar 

  7. Todd, J. A. et al. Science 240, 1003–1009 (1988).

    Article  CAS  ADS  Google Scholar 

  8. Gorga, J. C., Brown, J. H., Jardetzky, T., Wiley, D. C. & Strominger, J. L. Res. Immun. 142, 401–407 (1991).

    Article  CAS  Google Scholar 

  9. Gorga, J. C., Horejsí, V., Johnson, D. R., Raghupathy, R. & Strominger, J. L. J. biol. Chem. 262, 16087–16094 (1987).

    CAS  PubMed  Google Scholar 

  10. Stern, L. J. & Wiley, D. C. Cell 68, 465–477 (1992).

    Article  CAS  Google Scholar 

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

    Article  CAS  ADS  Google Scholar 

  12. Brown, J. H. et al. Nature 332, 845–850 (1988).

    Article  CAS  ADS  Google Scholar 

  13. Bricogne, G. Acta crystallogr. A32, 832–847 (1976).

    Article  CAS  ADS  Google Scholar 

  14. Sussman, J. L., Holbrook, S. R., Warrant, R. W., Church, G. M. & Kim, S.-H. J. molec. Biol. 123, 607–630 (1978).

    Article  CAS  Google Scholar 

  15. Falk, K., Rötzschke, O., Stevanovic, S., Jung, G. & Rammensee, H.-G. Nature 351, 290–296 (1991).

    Article  CAS  ADS  Google Scholar 

  16. Gorga, J. C. Crit. Rev. Immun. 11, 305–335 (1992).

    CAS  Google Scholar 

  17. Madden, D. R., Gorga, J. C., Strominger, J. L. & Wiley, D. C. Cell 70, 1035–1048 (1992).

    Article  CAS  Google Scholar 

  18. Silver, M. L., Guo, H.-C., Strominger, J. L. & Wiley, D. C. Nature 360, 367–369 (1992).

    Article  CAS  ADS  Google Scholar 

  19. Fremont, D. H., Matsumura, M., Stura, E. A., Peterson, P. A. & Wilson, I. A. Science 257, 919–927 (1992).

    Article  CAS  ADS  Google Scholar 

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

    Article  CAS  ADS  Google Scholar 

  21. Griffith, I. J. et al. J. exp. Med. 167, 541–555 (1988).

    Article  CAS  Google Scholar 

  22. Peccoud, J., Dellabona, P., Allen, P., Benoist, C. & Mathis, D. EMBO J. 9, 4215–4223 (1990).

    Article  CAS  Google Scholar 

  23. Sette, A. et al. J. Immun. 143, 3289–3294 (1989).

    CAS  PubMed  Google Scholar 

  24. Sidney, J. et al. J. Immun. 149, 2634–2640 (1992).

    CAS  PubMed  Google Scholar 

  25. Hammer, J., Takacs, B. & Sinigaglia, F. J. exp. Med. 176, 1007–1013 (1992).

    Article  CAS  Google Scholar 

  26. Geluk, A. et al. J. Immun. 149, 2864–2871 (1992).

    CAS  PubMed  Google Scholar 

  27. Racioppi, L., Ronchese, F., Schwartz, R. H. & Germain, R. N. J. Immun. 147, 3718–3727 (1991).

    CAS  PubMed  Google Scholar 

  28. Braunstein, N. S. & Germain, R. N. Proc. natn. Acad. Sci. U.S.A. 84, 2921–2925 (1987).

    Article  CAS  ADS  Google Scholar 

  29. Braunstein, N. S., Germain, R. N., Loney, K. & Berkowitz, N. J. Immun. 145, 1635–1645 (1990).

    CAS  PubMed  Google Scholar 

  30. Horn, G. T., Bugawan, T. L., Long, C. M. & Erlich, H. A. Proc. natn. Acad. Sci. U.S.A. 85, 6012–6016 (1988).

    Article  CAS  ADS  Google Scholar 

  31. Miyazaki, T. et al. Nature 345, 722–724 (1990).

    Article  CAS  ADS  Google Scholar 

  32. Slattery, R. M. et al. Nature 345, 724–726 (1990).

    Article  CAS  ADS  Google Scholar 

  33. Lund, T. et al., Nature 345, 727–729 (1990).

    Article  CAS  ADS  Google Scholar 

  34. Saper, M. A., Bjorkman, P. J. & Wiley, D. C. J. molec. Biol. 219, 277–319 (1991).

    Article  CAS  Google Scholar 

  35. Guo, H.-C. et al. Nature 360, 364–388 (1992).

    Article  CAS  ADS  Google Scholar 

  36. Jardetzky, T. S. et al. EMBO J. 9, 1797–1803 (1990).

    Article  CAS  Google Scholar 

  37. Busch, R., Hill, C. M., Haybali, J. D., Lamb, J. R. & Rothbard, J. B. J. Immun. 147, 1292–1298 (1991).

    CAS  PubMed  Google Scholar 

  38. DeMotz, S., Barbey, C., Corradin, G., Amoroso, A. & Lanzavecchia, A. Eur. J. Immun. 23, 425–432 (1993).

    Article  CAS  Google Scholar 

  39. Newton-Nash, D. K. & Eckels, D. D. J. Immun. 150, 1813–1821 (1993).

    CAS  PubMed  Google Scholar 

  40. Konig, R., Huang, L.-Y. & Germain, R. N. Nature 356, 796–798 (1992).

    Article  CAS  ADS  Google Scholar 

  41. Cammarota, G. et al. Nature 356, 799–801 (1992).

    Article  CAS  ADS  Google Scholar 

  42. Madden, D. R., Gorga, J. C., Strominger, J. L. & Wiley, D. C. Nature 353, 321–325 (1991).

    Article  CAS  ADS  Google Scholar 

  43. 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 

  44. Krieger, J. I. et al. J. Immun. 146, 2331–2340 (1991).

    CAS  PubMed  Google Scholar 

  45. Kropshofer, H., Bohlinger, I., Max, H. & Kalbacher, H. Biochemistry 30, 9177–9187 (1991).

    Article  CAS  Google Scholar 

  46. Klinman, N. R. J. exp. Med. 136, 241–260 (1972).

    Article  CAS  Google Scholar 

  47. Janeway, C. A. Jr et al. Cold Spring Harb. Symp. quant. Biol. 54, 657–666 (1989).

    Article  CAS  Google Scholar 

  48. Koulova, L., Clark, E. A., Shu, G. & DuPont, B. J. exp. Med. 173, 759–762 (1991).

    Article  CAS  Google Scholar 

  49. Nabavi, N. et al. Nature 360, 266–268 (1992).

    Article  CAS  ADS  Google Scholar 

  50. Schwartz, R. H. Cell 71, 1065–1068 (1992).

    Article  CAS  Google Scholar 

  51. Watts, T. H., Alaverdi, N., Wade, W. F. & Linsley, P. S. J. Immun. 150, 2192–2202 (1993).

    CAS  PubMed  Google Scholar 

  52. DeVos, A. M., Ultsch, M. & Kossiakoff, A. A. Science 255, 306–312 (1992).

    Article  CAS  ADS  Google Scholar 

  53. Kaye, J. & Janeway, C. A. Jr J. exp. Med. 159, 1397–1412 (1984).

    Article  CAS  Google Scholar 

  54. Roche, P. A., Marks, M. S. & Cresswell, P. Nature 354, 392–394 (1991).

    Article  CAS  ADS  Google Scholar 

  55. Springer, T. A., Kaufman, J. F., Terhorst, C. & Strominger, J. L. Nature 268, 213–218 (1977).

    Article  CAS  ADS  Google Scholar 

  56. Jencks, W. P. Proc. natn. Acad. Sci. U.S.A. 78, 4046–4050 (1981).

    Article  CAS  ADS  Google Scholar 

  57. Glaichenhaus, N., Shastri, N., Littman, D. R. & Turner, J. M. Cell 64, 511–520 (1991).

    Article  CAS  Google Scholar 

  58. DeMagistris, M. T. et al. Cell 68, 625–634 (1992).

    Article  CAS  Google Scholar 

  59. Alexander, J. et al. J. Immun. 150, 1–7 (1993).

    CAS  PubMed  Google Scholar 

  60. Racioppi, L., Ronchese, F., Matis, L. A. & Germain, R. J. exp. Med. 177, 1047–1060 (1993).

    Article  CAS  Google Scholar 

  61. Matsui, K., et al., Science 254, 1788–1791 (1991).

    Article  CAS  ADS  Google Scholar 

  62. Harrison, S. C. J. Appl. Crystallogr. 1, 84–89 (1968)

    Article  Google Scholar 

  63. Blum, M. Metcalf, P., Harrison, S. C. & Wiley, D. C. J. appl. Crystallogr. 20, 235–242 (1987).

    Article  CAS  Google Scholar 

  64. Stuart, D. & Artymiuk, P. Acta crystallogr. A40, 713–716 (1984).

    Article  CAS  Google Scholar 

  65. Teng, T.-Y. J. Appl. Crystallogr. 23, 387–391 (1990).

    Article  CAS  Google Scholar 

  66. Hodel, A., Kim, S.-H. & Brünger, A. T. Acta crystallogr. A48, 851–858 (1992).

    Article  CAS  Google Scholar 

  67. Jones, T. A. J. Appl. Crystallogr. 11, 268–272 (1978).

    Article  CAS  Google Scholar 

  68. Colman, P. M. Adv. Immun. 43, 99–132 (1988).

    Article  CAS  Google Scholar 

  69. Kwong, P. D. et al. Proc. natn. Acad. Sci. U.S.A. 87, 6423–6427 (1990).

    Article  CAS  ADS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts, 02138, USA

    Jerry H. Brown, Theodore S. Jardetzky, Joan C. Gorga, Lawrence J. Stern, Robert G. Urban, Jack L. Strominger & Don C. Wiley

  2. Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts, 02138, USA

    Jerry H. Brown, Lawrence J. Stern & Don C. Wiley

  3. Department of Pediatrics, Children's Hospital of Pittsburgh, 6130 Ranges Research Building, 3705 Fifth Avenue, Pittsburgh, Pennsylvania, 15213, USA

    Joan C. Gorga

Authors
  1. Jerry H. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Theodore S. Jardetzky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joan C. Gorga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lawrence J. Stern
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Robert G. Urban
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jack L. Strominger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Don C. Wiley
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brown, J., Jardetzky, T., Gorga, J. et al. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 364, 33–39 (1993). https://doi.org/10.1038/364033a0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/364033a0

  • Springer Nature Limited

This article is cited by

Search

Navigation