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Intermediate filaments vimentin and desmin share epitopes with M 1 protein of group A streptococci
S Birkholz1, P Goroncy-Bermes, M Schönermark
1Abt. Med. Mikrobiologie und Immunologie, Ruhr-Universität Bochum.
Abstract:
The cross reactivity of the murine monoclonal antibody PM II 40 against human glomeruli with streptococcal type 1 M protein was investigated. The antibody PM II 40 recognized a protective epitope on a glomerulonephritis-associated M type 1 strain. A 23 kD streptococcal surface protein extracted by limited pepsin digestion reacted with PM II 40 in the Western immunoblot. The aminoterminal sequence of this peptide was identical to the known aminoterminal amino acid sequence of type 1 M protein. Human renal podocytes carry the cross-reactive antigen of the antibody PM II 40 as could be shown by electron microscopy. The podocytes cultured from isolated human glomeruli showed a fibrillar pattern with the antibody in the immunofluorescence test. An anti-vimentin antibody and the antibody PM II 40 recognized the same proteins with molecular weights of 54, 52 and 43 kD of SDS-extracted isolated human glomeruli suggesting that vimentin is the glomerular antigen. The antibody PM II 40 not only react with vimentin but also with desmin suggesting that the recognized epitopes are distinct from that described by Kraus et al. for vimentin and type 1 M protein.
Insights
Murine monoclonal antibody PM II 40 cross-reacts with human kidney podocytes and streptococcal type 1 M protein. This suggests a potential link between streptococcal infections and glomerulonephritis via shared antigenic epitopes.
Area of Science:
- Immunology
- Nephrology
- Microbiology
Background:
- Streptococcal M proteins are implicated in post-infectious glomerulonephritis.
- Murine monoclonal antibody PM II 40 shows cross-reactivity with human glomeruli.
Purpose of the Study:
- To investigate the cross-reactivity of antibody PM II 40 with streptococcal type 1 M protein.
- To identify the glomerular antigen recognized by antibody PM II 40.
Main Methods:
- Western immunoblotting to detect protein interactions.
- Limited pepsin digestion of streptococcal surface protein.
- Electron microscopy and immunofluorescence testing on human renal podocytes.
- SDS-PAGE analysis of isolated human glomeruli.
Main Results:
- Antibody PM II 40 recognized a 23 kD streptococcal surface protein with an identical N-terminal sequence to type 1 M protein.
- Human renal podocytes express the cross-reactive antigen.
- Antibody PM II 40 and anti-vimentin antibody recognized similar molecular weight proteins (54, 52, 43 kD) in human glomeruli, suggesting vimentin as the antigen.
- Cross-reactivity with desmin was also observed.
Conclusions:
- The study identifies vimentin as a potential glomerular antigen cross-reactive with streptococcal type 1 M protein.
- Shared epitopes between M protein and glomerular vimentin/desmin may contribute to glomerulonephritis pathogenesis.
- Antibody PM II 40 provides a tool to study this cross-reactivity and its implications in kidney disease.