Loading...
Please wait, while we are loading the content...
Similar Documents
Anti-β2-Glycoprotein I Autoantibodies from Patients with the “Antiphospholipid” Syndrome Bind to β2-Glycoprotein I with Low Affinity: Dimerization of β2-Glycoprotein I Induces a Significant Increase in Anti-β2-Glycoprotein I Antibody Affinity
| Content Provider | Semantic Scholar |
|---|---|
| Author | Sheng, Yonghua Kandiah, David A. Krilis, Steven A. |
| Copyright Year | 1998 |
| Abstract | “Antiphospholipid” autoantibodies are associated with arterial and venous thrombosis, recurrent fetal loss, and thrombocytopenia. At present, the best-characterized antigenic target for these autoantibodies (or Abs) is the phospholipid-binding protein β 2 -glycoprotein I (β 2 GPI). These Abs bind β 2 GPI only in the presence of negatively charged phospholipids or microtiter polystyrene plates that have been specially treated to give the surface a negative charge. To determine whether the binding of these Abs to β 2 GPI on negatively charged surfaces is dependent on increased density or neo-epitopes formed as a consequence of a conformational change on β 2 GPI, we generated mutants of β 2 GPI by site-directed mutagenesis and assessed the binding characteristics of anti-β 2 GPI Abs to these mutants. Our results demonstrate that mutant F307*, which spontaneously forms significant dimerization, is bound best by all the anti-β 2 GPI Abs in an anti-β 2 GPI ELISA using irradiated polystyrene microtiter plates. In addition, these Abs bound mutant F307* coated onto standard polystyrene microtiter wells in the absence of phospholipid, whereas there was minimal binding with wild-type and mutant F307*/C288A, which formed minimal dimerization. Affinity-purified anti-β 2 GPI Abs from patients with the antiphospholipid syndrome demonstrated significantly higher binding affinity for mutant F307* in fluid phase than for wild-type or mutant F307*/C288A of β 2 GPI. These results demonstrate that autoantibody binding to β 2 GPI is intrinsically of low affinity and that the binding is dependent on the density of the Ag and not on neo-epitope formation. |
| Starting Page | 2038 |
| Ending Page | 2043 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Volume Number | 161 |
| Alternate Webpage(s) | http://www.jimmunol.org/content/jimmunol/161/4/2038.full.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
