GSBS Dissertations and Theses

Title

Mouse Antibody Response to Group A Streptococcal Carbohydrate: A Thesis

Approval Date

May 1989

Document Type

Doctoral Dissertation

Department

Graduate School of Biomedical Sciences, Immunology

Subjects

Mice; Streptococcus pyogenes; Streptococcal Infections; Antibody Formation; Academic Dissertations; Dissertations, UMMS

Abstract

In an attempt to more fully understand the generation of antibody diversity to carbohydrate antigens, we produced and characterized a panel of hybridoma cell lines specific for group A streptococcal carbohydrate from mice injected with the intact bacteria (minus the hyaluronic acid capsule and cell wall protein antigens). We have analyzed the use of heavy and light chain variable region genes in the early (day 7) and late response (hyperimmune) and have determined the nucleotide sequence of the dominant VH gene used in several of our hybridomas. Our data allowed us to assess the extent to which the recombination of various V, D, and J gene segments and somatic mutation contribute to antibody diversification in this system. In this report we confirm that a minimum of two VH and four VK gene segments are used to encode this response. We extend this analysis to show that multiple D and J gene segments are used and that a significant amount of junctional variability is tolerated in CDR 3. Our results also suggest that there is a positive selection for somatic mutation in CDR 1 during the hyperimmune response to group A streptococcal carbohydrate.

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