Molecular mimicry between streptococcal pyrogenic exotoxin B and endothelial cells

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1492-1506
Number of pages15
JournalLaboratory Investigation
Volume90
Issue number10
DOIs
Publication statusPublished - 2010 Oct 1

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Molecular Mimicry
B-Lymphocytes
Endothelial Cells
Monoclonal Antibodies
Bovine Serum Albumin
Heart Valves
Epitopes
Rheumatic Heart Disease
Complement Activation
Immunoglobulin G
erythrogenic toxin
Antigens
Amino Acids
Peptides
Passive Immunization
Acetylglucosamine
Antibodies
Glomerulonephritis
Streptococcus
Autoantibodies

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Molecular mimicry between streptococcal pyrogenic exotoxin B and endothelial cells",
abstract = "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.",
author = "Luo, {Yueh Hsia} and Chuang, {Woei Jer} and Wu, {Jiunn Jong} and Lin, {Ming T.} and Liu, {Ching Chuan} and Lin, {Pao Yen} and Roan, {Jun Neng} and Wong, {Tak Wah} and Chen, {Yuh Ling} and Lin, {Yee Shin}",
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Molecular mimicry between streptococcal pyrogenic exotoxin B and endothelial cells. / 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.

In: Laboratory Investigation, Vol. 90, No. 10, 01.10.2010, p. 1492-1506.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Molecular mimicry between streptococcal pyrogenic exotoxin B and endothelial cells

AU - Luo, Yueh Hsia

AU - Chuang, Woei Jer

AU - Wu, Jiunn Jong

AU - Lin, Ming T.

AU - Liu, Ching Chuan

AU - Lin, Pao Yen

AU - Roan, Jun Neng

AU - Wong, Tak Wah

AU - Chen, Yuh Ling

AU - Lin, Yee Shin

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AB - 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.

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