Multiple VH gene segments encode murine antistreptococcal antibodies.

Abstract

Most mouse strains are able to mount a diverse antibody response against group A streptococcal carbohydrate (GAC). Murine anti-GAC antibodies are for the most part restricted to IgM and IgG3 subclasses. Despite extensive heterogeneity in their isoelectric focusing patterns, > 50% of A/J anti-GAC antibodies share a common light chain defined by spectrotypic and idiotypic (V.kappa.lGAC) criteria. Protein and DNA sequencing strategies were used to examine the genetic basis of diversity in murine anti-GAC antibodies. Multiple, closely homologous VH gene segments contribute to the generation of anti-GAC antibodies, a common framework sequence, related to the V.kappa.27 subgroup, probably defines V.kappa.lGAC, and the A/J anti-GAC VH regions and BALB/c anti-inulin VH sequences are 95% homologous at the protein level and are likely encoded by overlapping VH gene families. The genetic mechanisms that might permit the evolution of multiple, closely homologous germline VH gene segments in the context of highly divergent flanking region sequences are discussed.