Journal article
Structural basis for autoantibody recognition of phosphatidylserine-β2 glycoprotein I and apoptotic cells
Proceedings of the National Academy of Sciences - PNAS, v 98(24), pp 13826-13831
20 Nov 2001
PMID: 11717440
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Apoptotic cells contain nuclear autoantigens that may initiate a systemic autoimmune response. To explore the mechanism of antibody binding to apoptotic cells, 3H9, a murine autoantibody with dual specificity for phospholipids and DNA, was used. H chain mutants of 3H9 were constructed, expressed as single-chain Fv (scFv) in
Escherichia coli
, and assessed for binding to phosphatidylserine, an antigen expressed on apoptotic cells. Both 3H9 and its germline revertant bound to dioleoyl phosphatidylserine in ELISA, and binding was enhanced by β2 glycoprotein I (β2GPI), a plasma protein that selectively binds to apoptotic cells. Higher relative affinity for DOPS-β2GPI was achieved by the introduction of Arg residues into the 3H9 H chain variable region at positions previously shown to mediate DNA binding. Specificity of the two structurally most diverse scFv for apoptotic cells was shown by flow cytometry, and two populations of scFv-bound cells were identified by differences in propidium iodide staining. The results suggest that, in autoimmunity, B cells with Ig receptors for apoptotic cells and DNA are positively selected, and that the antibodies they produce have the potential to affect the clearance and processing of apoptotic cells.
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Details
- Title
- Structural basis for autoantibody recognition of phosphatidylserine-β2 glycoprotein I and apoptotic cells
- Creators
- Brian A. Cocca - Hahnemann University HospitalSamarendra N. Seal - Drexel UniversityPaolo D'AgnilloYvonne M. Mueller - Drexel UniversityPeter D. Katsikis - Drexel UniversityJoyce Rauch - McGill UniversityMartin Weigert - Princeton UniversityMarko Z. Radic - Department of Microbiology, Immunology, and Biochemistry
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 98(24), pp 13826-13831
- Publisher
- The National Academy of Sciences
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000172328100065
- Scopus ID
- 2-s2.0-0035923534
- Other Identifier
- 991019348911204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology