on April 17, 2003
Published online before print April 17, 2003, doi: 10.1161/01.ATV.0000071701.62486.49
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Submitted on February 6, 2003
Accepted on February 21, 2003
Cross-Reactive B-Cell Epitopes of Microbial and Human Heat Shock Protein 60/65 in Atherosclerosis
Hannes Perschinka ;
From the Institute for Biomedical Aging Research (H.P., M.M., G.M., Q.X., G.W.), Austrian Academy of Sciences, Innsbruck, and the Institute of Pathophysiology (H.P., C.M., G.W.), University of Innsbruck Medical School, Innsbruck, Austria; the Institute of Infectious Diseases and Immunology (R.v.d.Z.), Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands; and the Department of Microbiology (S.G.M., R.P.M.), Montana State University, Bozeman, Mont.
* To whom correspondence should be addressed. E-mail: Georg.Wick{at}oeaw.ac.at.
Objective--Growing evidence suggests that immune reactions to heat shock protein 60 (HSP60) are involved in atherogenesis. Because of the high phylogenetic conservation between microbial and human HSP60, bacterial infections might be responsible for breaking the tolerance to self-HSP60, which is expressed on the surface of stressed arterial endothelial cells.
Methods and Results--We purified serum antibodies to Escherichia coli HSP60 (GroEL), the 60-kD chlamydial HSP, and HSP65 of Mycobacterium tuberculosis by affinity chromatography from clinically healthy subjects with sonographically proven carotid atherosclerosis. Reactivity of the purified antibodies with overlapping human HSP60 peptides was measured, and 8 shared common epitopes, recognized by all anti-bacterial HSP60/65 antibodies, were identified. Antisera specific for these cross-reactive epitopes were produced by immunizing rabbits with peptides derived from human HSP60. By immunohistochemistry, the epitopes were found to be present in the arterial wall of young subjects during the earliest stages of the disease.
Conclusions--Antibodies to microbial HSP60/65 recognize specific epitopes on human HSP60. These cross-reactive epitopes were shown to serve as autoimmune targets in incipient atherosclerosis and might provide further insights into the mechanisms of early atherogenesis.
Key words: antibodies • epitopes • autoimmunity • atherosclerosis • heat shock protein 60 • aging
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