Combinatorial diversity in the generation of antibody molecules. The complete amino-acid sequence of the variable domain of a monoclonal anti-streptococcal group A polysaccharide antibody.
The first complete amino-acid sequence of the variable region of the gamma 3 heavy chain from a murine anti-streptococcal group A polysaccharide (A-CHO) immunoglobulin (monoclonal antibody 2S1.3) is described. Therefore, in conjunction with the previously published 2S1.3 light chain sequence, a V kappa 25 structure, the entire variable domain of this antibody has been determined. In addition, four partial amino-terminal heavy chain sequences of other antibodies with the same specificity are reported. These heavy chains share a high degree of homology with heavy chains from fructosan-binding murine myeloma proteins with the exception of those positions known to be encoded by the D (diversity) segment in germ line DNA. The light chains associated with the heavy chains reported here are products of the V kappa 25, V kappa 27, and J kappa 5 genes. Up to date three VH and four V kappa subgroups have been shown to contribute genetic material to the assembly of antibodies specific for the A-CHO. Unlike other experimental systems employing structurally completely resolved full antigens the antistreptococcal immune response uses V genes previously shown to be involved in the formation of antibodies with different specificities. This provides further experimental evidence for the physiological relevance of heavy/light chain association as a posttranscriptional diversification mechanism in the generation of the antibody repertoire in addition to those somatic diversifiers acting directly upon the genes encoding the variable regions of individual chains.
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal; D003488:Cyanogen Bromide; D006825:Hybridomas / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D010446:Peptide Fragments / Q000032:analysis; D011135:Polysaccharides, Bacterial / Q000235:genetics / Q000276:immunology; D012689:Sequence Homology, Nucleic Acid; D013297:Streptococcus pyogenes / Q000276:immunology*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments; D011135:Polysaccharides, Bacterial; C006604:antistreptopolysaccharide; D003488:Cyanogen Bromide