title: An idiotypic marker associated with a germ-line encoded kappa light chain variable region that predominates the vaccine-induced human antibody response to the Haemophilus influenzae b polysaccharide.
abstract: Human antibodies specific for the Haemophilus influenzae b polysaccharide (Hib PS) frequently express a cross-reactive idiotype (CRI), and commonly utilize a VL region that is the product of the V kappa II gene A2. To examine further anti-Hib PS V region expression and to determine whether CRI expression is correlated with the V kappa IIA2 chain, we isolated a monoclonal antibody (MAb) reactive with an idiotypic determinant of anti-Hib PS antibodies. This MAb inhibited Hib PS binding but did not react with Ig isotypic determinants. The CRI recognized by this MAb, designated HibId-1, was associated with the Hib PS-combining site since the reactivity of the MAb with anti-Hib PS antibodies could be inhibited by Hib PS. HibId-1 was expressed by 17 of 17 clonally purified and sequence-defined anti-Hib PS antibodies having V kappa IIA2 L chains. In contrast, 0 of 10 anti-Hib PS antibodies having either V lambda, V kappa I, or V kappa III chains expressed HibId-1. Western blot analysis showed that the MAb anti-CRI reacted with isolated anti-Hib PS V kappa IIA2 L chains but not with H chains or other L chains, indicating that the HibId-1 determinant is localized to the V kappa IIA2 chain, and does not require pairing with H chain for expression. Anti-Hib PS antibodies bearing HibId-1 were present in at least 85% of subjects immunized with either free Hib PS or Hib PS coupled to diphtheria toxoid (Hib PS-DT), and comprised on the average 60% of the total vaccine-induced serum anti-Hib PS. HibId-1 expression was not related to age at vaccination inasmuch as infants, children, and adults had similar distributions of HibId-1-positive anti-Hib PS after vaccination with Hib PS-DT. HibId-1 was expressed at a lower frequency and comprised a smaller fraction of the total anti-Hib PS antibody in adult preimmunization sera as compared to post-Hib PS immunization sera, suggesting that immunization preferentially stimulates HibId-1-positive B cells. These data demonstrate that antibodies bearing HibId-1/V kappa IIA2 comprise a predominant component of the anti-Hib PS response induced by immunization, and that this pattern of VL expression is established early in ontogeny.
authors.affiliation: Children's Hospital Oakland Research Institute, California 94609.
authors.forename: A H
authors.initials: AH
authors.lastname: Lucas
authors.forename: R J
authors.initials: RJ
authors.lastname: Langley
authors.forename: D M
authors.initials: DM
authors.lastname: Granoff
authors.forename: M H
authors.initials: MH
authors.lastname: Nahm
authors.forename: M Y
authors.initials: MY
authors.lastname: Kitamura
authors.forename: M G
authors.initials: MG
authors.lastname: Scott
mesh_terms: D000328:Adult; D000367:Age Factors; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification; D016667:Bacterial Capsules; D001428:Bacterial Vaccines / Q000276:immunology*; D002648:Child; D018073:Haemophilus Vaccines; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000032:analysis*; D007135:Immunoglobulin Variable Region / Q000032:analysis* / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000032:analysis* / Q000235:genetics; D008969:Molecular Sequence Data; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001428:Bacterial Vaccines; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D011135:Polysaccharides, Bacterial