Abstract
Present understanding of the three-dimensional structure of antibody combining sites is based on X-ray diffraction studies of myeloma immunoglobulins (reviewed in refs 1, 2). The structures of the antigen-binding fragment (Fab) complexes of two of these immunoglobulins with small ligands have also been determined3,4. However, there is no crystallographic information concerning the interactions of an antibody with an antigen, nor do we know the precise structure of antigenic determinants on protein molecules (reviewed in ref. 5). We now report the first structure determination of an antigen–antibody complex at 6 Å resolution. The structure of the complex between hen egg-white lysozyme and the Fab of a monoclonal anti-lysozyme antibody (D1.3) shows that the combining site of antibodies is not merely a cleft delineated by the complementarity-determining regions of the variable regions of the light and heavy chains, but is a larger area extending beyond it. A correspondingly large area of the antigen makes close contacts with the antibody, in agreement with the notion of a ‘topographical’ rather than ‘sequential’ antigenic determinant. The structural basis of cross-reactivities of an antibody with heterologous antigens and the effect of a single amino acid substitution on antigenic specificity can thus be visualized in the structural model presented here.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Amzel, L. M. & Poljak, R. J. A. Rev. Biochem. 48, 961–997 (1979).
Davies, D. R. & Metzger, H. A. Rev. Immun. 1, 87–117 (1983).
Amzel, L. M., Poljak, R. J., Saul, F., Varga, J. M. & Richards, F. F. Proc. natn. Acad. Sci. U.S.A. 71, 1427–1430 (1974).
Segal, D. M. et al. Proc. natn. Acad. Sci. U.S.A. 71, 4298–4302 (1974).
Benjamin, D. C. et al. A. Rev. Immun. 2, 67–101 (1984).
Blake, C. C. F. et al. Nature 206, 757–761 (1965).
Arnon, R. in Immunochemistry of Enzymes and Their Antibodies (ed. Salton, M. R. J.) 1–28 (Wiley, New York, 1977).
Atassi, M. Z. Immunochemistry 15, 909–936 (1978).
White, T. J., Ibrahimi, I. M. & Wilson, A. C. Nature 274, 92–94 (1978).
Kobayashi, T. et al. Molec. Immun. 19, 619–630 (1982).
Smith-Gill, S. J., Lavoie, T. B. & Mainhart, C. R. J. Immun. 133, 384–393 (1984).
Meztger, D. W., Ch'ng, L. K., Miller, A. & Sercarz, E. E. Eur. J. Immun. 14, 87–93 (1984).
Mariuzza, R. A. et al. J. molec. Biol. 170, 1055–1058 (1983).
Bricogne, G. in Computational Crystallography (ed. Sayre, D.) 223–230 (Oxford University Press, 1982).
Poljak, R. J., Amzel, L. M., Avey, H. P., Becka, L. N. & Nisonoff, A. Nature new Biol. 235, 137–140 (1972).
Jones, T. A. J. appl. Crystallogr. 11, 268–272 (1978).
Poljak, R. J. et al. Proc. natn. Acad. Sci. U.S.A. 70, 3305–3310 (1973).
Matsushima, M. et al. Molec. Biol. 121, 441–459 (1978).
Kabat, E. A. & Wu, T. T. Ann. N.Y. Acad. Sci. 190, 382–392 (1971).
Ibrahimi, I. M., Prager, E. M., White, T. J. & Wilson, A. C. Biochemistry 18, 2736–2743 (1979).
Ibrahimi, I. M., Eder, J., Prager, E. M., Wilson, A. C. & Arnon, R. Molec. Immun. 17, 37–46 (1980).
LaRue, J. N. & Speck, J. C. Jr J. biol. Chem. 245, 1985–1991 (1970).
Kaneda, M., Kato, I., Tominaga, N., Titani, K. & Narita, K. J. Biochem., Tokyo 66, 747–749 (1969).
Lamoyi, E., Estess, P., Capra, J. D. & Nisonoff, A. J. Immun. 124, 2834–2840 (1980).
Westhof, E. et al. Nature 311, 123–126 (1984).
Tainer, J. A. et al. Nature 312, 127–134 (1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Amit, A., Mariuzza, R., Phillips, S. et al. Three-dimensional structure of an antigen–antibody complex at 6 Å resolution. Nature 313, 156–158 (1985). https://doi.org/10.1038/313156a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/313156a0
This article is cited by
-
Antigenic Structure of the Human Muscle Nicotinic Acetylcholine Receptor Main Immunogenic Region
Journal of Molecular Neuroscience (2010)
-
PEPOP: Computational design of immunogenic peptides
BMC Bioinformatics (2008)
-
Structural studies of an HLA-A03 alloantigenic epitope defined by a human hybridoma antibody
Immunogenetics (1989)
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.