title: Immunoglobulin light chain variable region gene sequences for human antibodies to Haemophilus influenzae type b capsular polysaccharide are dominated by a limited number of V kappa and V lambda segments and VJ combinations.
abstract: The immune repertoire to Haemophilus influenzae type b capsular polysaccharide (Hib PS) appears to be dominated by certain light chain variable region genes (IgVL). In order to examine the molecular basis underlying light chain bias, IgVL genes have been cloned from a panel of heterohybridomas secreting human anti-Hib PS (antibody) (anti-Hib PS Ab). One hybridoma, representative of the predominant serum clonotype of anti-Hib PS Ab in older children and adults following immunization or Hib infection, uses a V kappa II segment identical to the germline gene A2, and a JK3 segment. A second kappa hybridoma uses a member of the V kappa I family and a JK4 segment. Four lambda antibodies, all cross-reactive with the structurally related antigen Escherichia coli K100 PS, use V lambda VII segments which are 96-98% homologous to one another, and may originate from a single germline gene. Two additional lambda antibodies, not K100-cross-reactive, are encoded by members of the V lambda II family. All lambda antibodies use highly homologous J lambda 2 or J lambda 3 segments. The VJ joints of all lambda antibodies and the V kappa II-encoded antibody are notable for the presence of an arginine codon, suggesting an important role in antigen binding. Although more complex than heavy chain variable region gene usage, a significant portion of serum anti-Hib PS Ab is likely to be encoded by a limited number of V kappa and V lambda segments and VJ combinations, which may be selectively expressed during development, or following antigen exposure.
authors.affiliation: Division of Infectious Diseases, Washington University School of Medicine, St. Louis Children's Hospital, Missouri 63110.
authors.forename: E E
authors.initials: EE
authors.lastname: Adderson
authors.forename: P G
authors.initials: PG
authors.lastname: Shackelford
authors.forename: R A
authors.initials: RA
authors.lastname: Insel
authors.forename: A
authors.initials: A
authors.lastname: Quinn
authors.forename: P M
authors.initials: PM
authors.lastname: Wilson
authors.forename: W L
authors.initials: WL
authors.lastname: Carroll
mesh_terms: D000328:Adult; D000367:Age Factors; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000235:genetics*; D016667:Bacterial Capsules; D001428:Bacterial Vaccines / Q000276:immunology*; D001483:Base Sequence; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D005803:Genes, Immunoglobulin; D018073:Haemophilus Vaccines; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D011135:Polysaccharides, Bacterial / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D011135:Polysaccharides, Bacterial