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Chapter 7 : Peptide Mimicry of Streptococcal Group A Carbohydrate

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Abstract:

This chapter explores the immunochemical relationships, as defined by antibodies, between the cell wall polysaccharide of (group A streptococci) and peptides. It provides basic information on the structure and immunobiology of the streptococcal cell wall polysaccharide (group A carbohydrate [GAC]). Following comments on the nature of molecular mimicry in general, an overview of prior studies on the cross-reactions between GAC and epitopes on host structures is provided. The next two sections review studies of antibody cross-reactivity between GAC and peptides either that correspond in amino acid sequence to host proteins or that are derived from combinatorial peptide libraries. Molecular analysis of human monoclonal antibodies cross-reactive with -acetyl-β-D-glucosamine (GlcNAc) and peptides revealed that they used a variety of variable-region genes and exhibited little evidence of antigen-driven somatic mutations. It remains unknown if GlcNAc-specific antibodies are pathogenic and, if so, what structural features predispose the antibodies to pathogenicity. Researchers used the phage-display approach to investigate peptide mimicry of GAC with respect to five GAC-specific monoclonal antibodies, including the murine monoclonal antibody HGAC 39.G3. This antibody (IgG3, kappa chain) was generated with the group A vaccine (GAV; heat-killed, pepsin-treated ) as the immunogen and has specificity for the GlcNAc residues of group A carbohydrate.

Citation: Greenspan N, Pinilla C, Shikhman A. 2000. Peptide Mimicry of Streptococcal Group A Carbohydrate, p 83-94. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch7

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Figure 1

Molecular structures of Ac-yryygl-NH (molecular weight, 876; top) and GlcNAc (molecular weight, 221; bottom).

Citation: Greenspan N, Pinilla C, Shikhman A. 2000. Peptide Mimicry of Streptococcal Group A Carbohydrate, p 83-94. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch7
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References

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Tables

Generic image for table
Table 1

Relative affinities for analogs of Ac-yryygl-NH recognized by monoclonal antibody HGAC 39.G3

Citation: Greenspan N, Pinilla C, Shikhman A. 2000. Peptide Mimicry of Streptococcal Group A Carbohydrate, p 83-94. In Cunningham M, Fujinami R (ed), Molecular Mimicry, Microbes, and Autoimmunity. ASM Press, Washington, DC. doi: 10.1128/9781555818074.ch7

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