Molecular mimicry between streptococcal pyrogenic exotoxin B and endothelial cells

Yueh Hsia Luo, Woei Jer Chuang, Jiunn Jong Wu, Ming T. Lin, Ching Chuan Liu, Pao Yen Lin, Jun Neng Roan, Tak Wah Wong, Yuh Ling Chen, Yee Shin Lin

研究成果: Article同行評審

16 引文 斯高帕斯(Scopus)

摘要

Molecular mimicry between group A streptococcus and host antigens has important roles in the development of post-streptococcal sequelae, including glomerulonephritis and rheumatic heart disease (RHD). The etiology of RHD involves host cross-reactivity with M proteins and carbohydrate antigens. In this study, we show that anti-streptococcal pyrogenic exotoxin B (SPE B) antibodies exhibited characteristics of autoantibodies, which cross-react with endothelial cells. Immunoglobulin G (IgG) deposition and complement activation were observed in the heart valve of SPE B-immunized mice. In addition, apoptosis in the heart valve was detected in SPE B-immunized mice. An anti-SPE B monoclonal antibody (mAb) 10G showed cross-reactivity with human microvascular endothelial (HMEC-1) cells and mouse valve endothelial cells. Passive immunization with mAb 10G also caused IgG deposition, complement activation, and apoptotic cell death in the mouse heart valve. We conducted peptide array and ELISA using synthetic peptides to identify the SPE B antigenic epitope recognized by mAb 10G. Results showed that the major epitope of mAb 10G is localized to amino-acid residues 296-310 of SPE B (P7-8). The cross-reactivity of mAb 10G with endothelial cells was inhibited using P7-8 peptides for competition. These results suggest that anti-SPE B antibodies cross-react with endothelial cells, and that a dominant epitope is located within the amino-acid residues 296-310 of SPE B. Moreover, we found that mAb 10G can also bind to N-acetyl-Β-D-glucosamine (GlcNAc) conjugated with bovine serum albumin (BSA), but not to BSA or M1 protein. Competition assay showed that the binding activity of mAb 10G with GlcNAc-BSA and P7-8 of SPE B was inhibited by pretreatment with GlcNAc-BSA or P7-8 peptides. Therefore, our results suggest that conformational molecular mimicry may exist between SPE B and GlcNAc.

原文English
頁(從 - 到)1492-1506
頁數15
期刊Laboratory Investigation
90
發行號10
DOIs
出版狀態Published - 2010 十月

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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