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Mouse antibody response to group A streptococcal carbohydrate
C D Jarvis1, L E Cannon, J Stavnezer
1Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655.
Journal of Immunology (Baltimore, Md. : 1950)
|December 15, 1989
Summary
This study reveals how antibody diversity is generated against group A streptococcal carbohydrate antigens. It highlights the specific gene segments and mutations involved in the immune response.
Area of Science:
- Immunology
- Microbial Pathogenesis
Background:
- Antibody diversity is crucial for effective immune responses against pathogens.
- Group A Streptococcus (GAS) possesses carbohydrate antigens that elicit an immune response.
- Understanding antibody generation to GAS carbohydrate antigens is key to vaccine development.
Purpose of the Study:
- To investigate the molecular mechanisms underlying antibody diversity generation against GAS carbohydrate antigens.
- To analyze the usage of V, D, and J gene segments and somatic mutation in this immune response.
- To identify specific antibody features selected during the hyperimmune response.
Main Methods:
- Production and characterization of hybridoma cell lines specific for GAS carbohydrate antigens.
- Analysis of heavy (H) and light (L) chain V region gene usage.
- Sequencing of dominant VH genes and assessment of somatic mutation levels.
Main Results:
- A minimum of two VH and four VK gene segments are utilized.
- Multiple D and J gene segments are employed, with significant junctional variability in CDR3.
- Somatic mutation levels in the hyperimmune response are generally low compared to haptens and protein antigens.
- Positive selection for mutations in CDR1 during the hyperimmune response to GAS carbohydrate antigens was observed.
Conclusions:
- The study confirms the combinatorial diversity generated by V, D, J recombination and junctional variability.
- It suggests a limited role for somatic mutation in this specific antibody response, contrasting with other antigen types.
- Evidence points to positive selection acting on specific regions (CDR1) of the antibody V-genes during the hyperimmune response to GAS carbohydrate antigens.