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

Arterioscler Thromb Vasc Biol. 2003 Jun 1;23(6):1060-5. doi: 10.1161/01.ATV.0000071701.62486.49. Epub 2003 Apr 17.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Bacterial / immunology
  • Arteriosclerosis / immunology*
  • B-Lymphocytes / immunology*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / immunology*
  • Chaperonin 60 / chemistry
  • Chaperonin 60 / immunology*
  • Chaperonins / chemistry
  • Chaperonins / immunology*
  • Chlamydia trachomatis / immunology
  • Cross Reactions
  • Epitopes / chemistry
  • Epitopes / immunology*
  • Escherichia coli / immunology
  • Humans
  • Male
  • Models, Molecular
  • Molecular Sequence Data
  • Mycobacterium tuberculosis / immunology
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / immunology
  • Rabbits
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Species Specificity

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Chaperonin 60
  • Epitopes
  • Peptide Fragments
  • heat-shock protein 65, Mycobacterium
  • Chaperonins