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Specificity pockets for the side chains of peptide antigens in HLA-Aw68

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Abstract

WE have determined the structure of a second human histocompati-bility glycoprotein, HLA-Aw68, by X-ray crystallography and refined it to a resolution of 2.6 Å. Overall, the structure is extremely similar to that of HLA-A2 (refs 1, 2; and M.A.S. et al., manuscript in preparation), although the 11 amino-acid substitutions at polymorphic residues3,4 in the antigen-binding cleft2 alter the detailed shape and electrostatic charge of that site. A prominent negatively charged pocket within the cleft extends underneath the α-helix of the α1-domain, providing a potential subsite for recognizing a positively charged side chain or peptide N terminus. Uninterpreted electron density, presumably representing an unknown 'antigen(s)', which seems to be different from that seen in the HLA-A2 structure1, occupies the cleft and extends into the negatively charged pocket in HLA-Aw68. The structures of HLA-Aw68 and HLA-A2 demonstrate how polymorphism creates and alters subsites (pockets) positioned to bind peptide side chains, thereby suggesting the structural basis for allelic specificity in foreign antigen binding.

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Author notes

  1. P. J. Bjorkman

    Present address: Division of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California, USA

  2. D. C. Wiley: To whom correspondence should be addressed.

Authors and Affiliations

  1. Department of Biochemistry, Harvard University, Cambridge, Massachusetts, 02138, USA

    P. J. Bjorkman & J. L. Strominger

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

    T. P. J. Garrett, M. A. Saper & D. C. Wiley

Authors
  1. T. P. J. Garrett
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  2. M. A. Saper
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  3. P. J. Bjorkman
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  4. J. L. Strominger
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  5. D. C. Wiley
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Garrett, T., Saper, M., Bjorkman, P. et al. Specificity pockets for the side chains of peptide antigens in HLA-Aw68. Nature 342, 692–696 (1989). https://doi.org/10.1038/342692a0

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