Cross-reactive B-cell epitopes of microbial and human heat shock protein 60/65 in atherosclerosis.
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.


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.
Perschinka
Hannes
H
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Peter-Mayr-Strasse 4b, 6020 Innsbruck, Austria.
Mayr
Manuel
M
Millonig
Gunda
G
Mayerl
Christina
C
van der Zee
Ruurd
R
Morrison
Sandra G
SG
Morrison
Richard P
RP
Xu
Qingbo
Q
Wick
Georg
G
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001161:Arteriosclerosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D018834:Chaperonin 60 / Q000737:chemistry / Q000276:immunology*; D018833:Chaperonins / Q000737:chemistry / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000276:immunology; D003429:Cross Reactions; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D011817:Rabbits; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D000939:Epitopes; D010446:Peptide Fragments; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins