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Human antibodies to group A streptococcal carbohydrate. Ontogeny, subclass restriction, and clonal diversity
P G Shackelford1, S J Nelson, A T Palma
1Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
Insights
Children’s immune responses to Streptococcus pyogenes polysaccharides mature early, showing distinct antibody subclasses (IgG1 and IgG2) compared to adults. Antibody diversity increases with age, indicating developing immune competence in young children.
Area of Science:
- Immunology
- Microbiology
- Pediatrics
Background:
- Young children often exhibit temporary immune-incompetence to certain antigens.
- Streptococcus pyogenes is a common pathogen with well-defined polysaccharide and protein antigens.
Purpose of the Study:
- To investigate the maturation of antibody responses to polysaccharide and protein antigens of Streptococcus pyogenes in children.
- To characterize qualitative differences in antibody responses between children and adults.
Main Methods:
- Studied antibodies to polysaccharide (A-CHO) and protein antigens of Streptococcus pyogenes.
- Analyzed antibody subclasses (IgG1, IgG2) and clonal diversity in children and adults.
- Examined antibody responses in convalescent sera after infection.
Main Results:
- Antibody responses to S. pyogenes polysaccharide antigens mature in parallel with or earlier than responses to protein antigens in children over 2 years old.
- Adult antibodies to A-CHO are restricted to IgG2, while children's antibodies are found in both IgG1 and IgG2 subclasses.
- Clonal diversity of anti-A-CHO antibodies increases with age, with new clonotypes appearing post-infection.
Conclusions:
- Children develop immune competence to polysaccharide antigens, with distinct antibody subclass profiles compared to adults.
- The immune system demonstrates adaptability, generating diverse antibody responses post-infection across different age groups.
Abstract:
To investigate immuno-incompetence to polysaccharide Ag in young children, antibodies to the polysaccharide and protein Ag of Streptococcus pyogenes were studied. S. pyogenes was chosen because it commonly causes natural infections and has well-characterized polysaccharide and protein Ag. In children over the age of 2 yr it was found that the maturation of antibody responses to the polysaccharide Ag of S. pyogenes (A-CHO) appeared to occur in parallel with, or even earlier, than the responses to streptococcal protein Ag. When antibodies to group A carbohydrate (A-CHO) were studied in detail, qualitative differences between the antibodies of children and adults were demonstrated. Although anti-A-CHO antibodies of adults were strikingly restricted to the IgG2 subclass, those of children were found in both the IgG1 and IgG2 subclasses. In addition, the clonal diversity of IgG antibodies to A-CHO increased with age, and additional clonotypes were detectable in convalescent sera of some subjects of all ages after infection. Two cases with major additional clonotypes after group A streptococcal infection were studied in detail. In these two cases the additional clonotypes belonged to a different IgG subclass than the previously dominant clonotypes, and the expression of the additional major clonotypes occurred in both IgG1 and IgG2 subclasses.