Molecular mimicry between streptococcal pyrogenic exotoxin B and endothelial cells

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

来源：Laboratory Investigation, 2010, 90(10): 1492-1506.

DOI：10.1038/labinvest.2010.93

Molecular mimicry between group A streptococcus and host antigens has important roles in the development of poststreptococcal 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-b-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. Laboratory Investigation (2010) 90, 1492-1506; doi: 10.1038/labinvest.2010.93; published online 10 May 2010

• 出版日期2010-10