International Immunology, Vol. 13, No. 10, 1335-1343,
October 2001
© 2001 Japanese Society for Immunology
Antibody levels to the class I and II epitopes of the M protein and myosin are related to group A streptococcal exposure in endemic populations
1 CRC for Vaccine Technology, The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, and the Australian Centre for International and Tropical Health and Nutrition, University of Queensland, Brisbane 4029, Australia
2 Department of Experimental Medicine, Post-graduate Institute of Medical Education and Research, Chandigarh, India 160012
3 Menzies School of Health Research, Casuarina, NT 0810, Australia
4 King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
5 Department of Microbiology, Chiang Mai University, Chiang Mai 50002, Thailand
Correspondence to: Correspondence to: M. F. Good
Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal glomerulonephritis are thought to be autoimmune diseases, and follow group A streptococcal (GAS) infection. Different GAS M types have been associated with rheumatogenicity or nephritogenicity and categorized into either of two distinct classes (I or II) based on amino acid sequences present within the repeat region (`C' repeats) of the M protein. Sera from ARF patients have previously been shown to contain elevated levels of antibodies to the class I-specific epitope and myosin with the class I-specific antibodies also being cross-reactive to myosin, suggesting a disease association. This study shows that immunoreactivity of the class I-specific peptide and myosin does not differ between controls and acute RF (ARF)/RHD in populations that are highly endemic for GAS, raising the possibility that the association is related to GAS exposure, not the presence of ARF/RHD. Peptide inhibition studies suggest that the class I epitope may be conformational and residue 10 of the peptide is critical for antibody binding. We demonstrate that correlation of antibody levels between the class I and II epitope is due to class II-specific antibodies recognizing a common epitope with class I which is contained within the sequence RDL-ASRE. Our results suggest that antibody prevalence to class I and II epitopes and myosin is associated with GAS exposure, and that antibodies to these epitopes are not an indicator of disease nor a pathogenic factor in endemic populations.
Keywords: antibodies, autoimmunity, infectious immunity bacteria