This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Metzler, B. Articles by Wick, G. Search for Related Content PubMed PubMed Citation Articles by Metzler, B. Articles by Wick, G.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:536-541.)
© 1997 American Heart Association, Inc.

Articles

Epitope Specificity of Anti–Heat Shock Protein 65/60 Serum Antibodies in Atherosclerosis

Bernhard Metzler; Georg Schett; Roman Kleindienst; Ruurd van der Zee; Tom Ottenhoff; Ali Hajeer; Robert Bernstein; Qingbo Xu; ; Georg Wick

From the Institute for Biomedical Aging Research, Austrian Academy of Sciences (B.M., G.S., R.K., Q.X., G.W.), the Institute for General and Experimental Pathology, University of Innsbruck Medical School (B.M., G.S., G.W.), and the Department of Internal Medicine, University Hospital (R.K.), Innsbruck, Austria; the Institute for Infectious Diseases and Immunology, Faculty of Veterinary Medicine Utrecht (R. van der Z.), and the Department of Immunohematology and Blood Bank, University Hospital Leiden (T.O.), The Netherlands; and the Department of Rheumatology, University of Manchester Medical School, UK (A.H., R.B.).

Correspondence to Dr Georg Wick, Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, A-6020 Innsbruck, Austria. E-mail bioage-c511{at}uibk.ac.at.

Abstract Levels of specific antibodies (Ab) against mycobacterial and human heat shock protein (hsp) 65/60 are increased in the sera of patients with atherosclerotic lesions and have been demonstrated to be capable of mediating endothelial cytotoxicity. To clarify the antigen epitopes recognized by these serum Abs, Ab binding to hsp65 deletion mutants (Dms), as well as to overlapping 15-mer and 8-mer hsp65 peptides, was assessed. Western blotting of hsp65 Dms indicated the presence of at least one epitope between amino acid (aa) residues 171and 276, recognized by both high-titer sera and affinity-purified anti-hsp65/60 Ab. Fluorescence immunoassays using 53 15-mer peptides and Pin ELISA using 526 7-mer peptides demonstrated three distinct, conserved sequences with high affinity to high-titer sera and purified anti-hsp65/60 Ab. Two N-terminal sequences, aa 97-109 and aa 179-187, and one C-terminal sequence, aa 504-512, were identified. These three epitopes recognized by anti-hsp65/60 Ab may serve as autoantigens in certain circumstances in vivo. This phenomenon could contribute to the initiation of atherosclerosis by an autoimmune reaction.

Key Words: atherosclerosis • heat shock protein • antibodies • epitope specificity • autoimmunity

This article has been cited by other articles:

				G. Foteinos, A. R. Afzal, K. Mandal, M. Jahangiri, and Q. Xu Anti-Heat Shock Protein 60 Autoantibodies Induce Atherosclerosis in Apolipoprotein E-Deficient Mice via Endothelial Damage Circulation, August 23, 2005; 112(8): 1206 - 1213. [Abstract] [Full Text] [PDF]

				J.-I. Choi, S.-W. Chung, H.-S. Kang, B.Y. Rhim, Y.-M. Park, U.-S. Kim, and S.-J. Kim Epitope Mapping of Porphyromonas gingivalis Heat-shock Protein and Human Heat-shock Protein in Human Atherosclerosis Journal of Dental Research, December 1, 2004; 83(12): 936 - 940. [Abstract] [Full Text] [PDF]

				K. Uray, F. Hudecz, G. Fust, and Z. Prohaszka Comparative analysis of linear antibody epitopes on human and mycobacterial60-kDa heat shock proteins using samples of healthy blood donors Int. Immunol., October 1, 2003; 15(10): 1229 - 1236. [Abstract] [Full Text] [PDF]

				H. Perschinka, M. Mayr, G. Millonig, C. Mayerl, R. van der Zee, S. G. Morrison, R. P. Morrison, Q. Xu, and G. Wick Cross-Reactive B-Cell Epitopes of Microbial and Human Heat Shock Protein 60/65 in Atherosclerosis Arterioscler Thromb Vasc Biol, June 1, 2003; 23(6): 1060 - 1065. [Abstract] [Full Text] [PDF]

				A. G. Pockley Heat Shock Proteins, Inflammation, and Cardiovascular Disease Circulation, February 26, 2002; 105(8): 1012 - 1017. [Full Text] [PDF]

				A. G. Pockley, R. Wu, C. Lemne, R. Kiessling, Ulf de Faire, and J. Frostegard Circulating Heat Shock Protein 60 Is Associated With Early Cardiovascular Disease Hypertension, August 1, 2000; 36(2): 303 - 307. [Abstract] [Full Text] [PDF]

				M. Mosorin, H.-M. Surcel, A. Laurila, M. Lehtinen, R. Karttunen, J. Juvonen, J. Paavonen, R. P. Morrison, P. Saikku, and T. Juvonen Detection of Chlamydia pneumoniae-Reactive T Lymphocytes in Human Atherosclerotic Plaques of Carotid Artery Arterioscler Thromb Vasc Biol, April 1, 2000; 20(4): 1061 - 1067. [Abstract] [Full Text] [PDF]

				Z. Prohaszka, J. Duba, G. Lakos, E. Kiss, L. Varga, L. Janoskuti, A. Csaszar, I. Karadi, K. Nagy, M. Singh, et al. Antibodies against human heat-shock protein (hsp) 60 and mycobacterial hsp65 differ in their antigen specificity and complement-activating ability Int. Immunol., September 1, 1999; 11(9): 1363 - 1370. [Abstract] [Full Text] [PDF]

				G. Schett, B. Metzler, R. Kleindienst,, A. Amberger, H. Recheis, Q. Xu, and G. Wick Myocardial injury leads to a release of heat shock protein (hsp) 60 and a suppression of the anti-hsp65 immune response Cardiovasc Res, June 1, 1999; 42(3): 685 - 695. [Abstract] [Full Text] [PDF]