The low-affinity immunoglobulin E (IgE) receptor, CD23 (FcεRII), binds both IgE and CD21 and, through these interactions, regulates the synthesis of IgE, the antibody isotype that mediates the allergic response. We have determined the three-dimensional structure of the C-type lectin domain of CD23 in solution by nuclear magnetic resonance spectroscopy. An analysis of concentration-dependent chemical shift perturbations have allowed us to identify the residues engaged in self-association to the trimeric state, whereas ligand-induced changes have defined the binding sites for IgE and CD21. The results further reveal that CD23 can bind both ligands simultaneously. Despite the C-type lectin domain structure, none of the interactions require calcium. We also find that IgE and CD23 can interact to form high molecular mass multimeric complexes. The interactions that we have described provide a solution to the paradox that CD23 is involved in both up- and down-regulation of IgE and provide a structural basis for the development of inhibitors of allergic disease.
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19 September 2005
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September 19 2005
The structure of human CD23 and its interactions with IgE and CD21
Richard G. Hibbert,
Richard G. Hibbert
1Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, England, UK
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Peter Teriete,
Peter Teriete
1Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, England, UK
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Gabrielle J. Grundy,
Gabrielle J. Grundy
2Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, England, UK
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Rebecca L. Beavil,
Rebecca L. Beavil
2Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, England, UK
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Rajko Reljić,
Rajko Reljić
2Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, England, UK
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V. Michael Holers,
V. Michael Holers
3Department of Medicine, Health Science Center, University of Colorado, Denver, CO 80262
4Department of Immunology, Health Science Center, University of Colorado, Denver, CO 80262
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Jonathan P. Hannan,
Jonathan P. Hannan
3Department of Medicine, Health Science Center, University of Colorado, Denver, CO 80262
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Brian J. Sutton,
Brian J. Sutton
2Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, England, UK
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Hannah J. Gould,
Hannah J. Gould
2Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, England, UK
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James M. McDonnell
James M. McDonnell
1Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, England, UK
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Richard G. Hibbert
1Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, England, UK
Peter Teriete
1Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, England, UK
Gabrielle J. Grundy
2Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, England, UK
Rebecca L. Beavil
2Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, England, UK
Rajko Reljić
2Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, England, UK
V. Michael Holers
3Department of Medicine, Health Science Center, University of Colorado, Denver, CO 80262
4Department of Immunology, Health Science Center, University of Colorado, Denver, CO 80262
Jonathan P. Hannan
3Department of Medicine, Health Science Center, University of Colorado, Denver, CO 80262
Brian J. Sutton
2Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, England, UK
Hannah J. Gould
2Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, England, UK
James M. McDonnell
1Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, England, UK
CORRESPONDENCE James M. McDonnell: [email protected]
Abbreviations used: CTLD, C-type lectin-like domain; D, dalton; MBP, mannose-binding protein; NMR, nuclear magnetic resonance; NOE, nuclear overhauser effect; ppm, parts per million, r.m.s., root mean squared.
G.J. Grundy's present address is Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Received:
April 22 2005
Accepted:
August 01 2005
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 202 (6): 751–760.
Article history
Received:
April 22 2005
Accepted:
August 01 2005
Citation
Richard G. Hibbert, Peter Teriete, Gabrielle J. Grundy, Rebecca L. Beavil, Rajko Reljić, V. Michael Holers, Jonathan P. Hannan, Brian J. Sutton, Hannah J. Gould, James M. McDonnell; The structure of human CD23 and its interactions with IgE and CD21 . J Exp Med 19 September 2005; 202 (6): 751–760. doi: https://doi.org/10.1084/jem.20050811
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