Clonal characterization of the human IgG antibody repertoire to Haemophilus influenzae type b polysaccharide. IV. The less frequently expressed VL are heterogeneous

J Immunol. 1991 Dec 1;147(11):4007-13.

Abstract

We previously demonstrated that the human anti-Haemophilus influenzae type b polysaccharide (Hib-PS) VL repertoire is dominated by a product of the V kappa II gene, A2, and that V kappa II-A2 anti-Hib-PS antibodies have little or no somatic mutation in VL. To further study this VL repertoire, we studied non-A2 anti-Hib-PS antibodies that were identified either serologically or by amino-terminal amino acid sequence analysis. Of 15 non-A2 anti-Hib-PS antibodies from 12 vaccinated adults, we found four V lambda, five V kappa I, one non-A2 V kappa II, four V kappa III, and one V kappa IV antibodies. As expected, all but two of these subjects also produced V kappa II-A2 antibodies. Interestingly, one of these subjects lacks the A2 gene in the germ line. However, both subjects who did not produce detectable V kappa II antibody did produce normal amounts of total anti-Hib-PS antibody after vaccination. Candidate V kappa genes for the non-A2 antibodies were identified by comparison of up to 60 VL amino acid residues, including CDR1 and CDR2, with all sequenced V kappa genes. V kappa I antibodies appear to be products of three newly sequenced V kappa I genes, O8, O18, and L11, that are reported here. The O8 and O18 genes encode identical amino acid sequences. The non-A2 V kappa II antibody is a likely product of the A1 or A17 genes, the V kappa III antibodies are likely products of the A27 gene, and the V kappa IV antibody is a product of the single V kappa IV gene, B3. Unlike V kappa II-A2 antibodies, the V kappa I, V kappa III, and V kappa IV antibodies differed by one to five CDR residues from the germ line product of the candidate genes, suggesting the presence of somatic mutations. Thus, anti-Hib-PS antibodies can be divided into two types, the most frequently observed A2 antibodies with little or no somatic mutation and non-A2 antibodies that likely contain somatic mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Bacterial / chemistry*
  • Antibodies, Bacterial / genetics
  • Antibody Diversity
  • Base Sequence
  • Clone Cells
  • Genes, Immunoglobulin*
  • Haemophilus influenzae / immunology*
  • Humans
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / genetics
  • Immunoglobulin Variable Region / chemistry
  • Immunoglobulin Variable Region / genetics*
  • Immunoglobulin kappa-Chains / chemistry
  • Immunoglobulin kappa-Chains / genetics*
  • Molecular Sequence Data
  • Polysaccharides, Bacterial / immunology*
  • Restriction Mapping

Substances

  • Antibodies, Bacterial
  • Immunoglobulin G
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains
  • Polysaccharides, Bacterial

Associated data

  • GENBANK/M64855
  • GENBANK/M64856
  • GENBANK/M64857
  • GENBANK/M64858
  • GENBANK/M96138
  • GENBANK/M96139
  • GENBANK/M96140
  • GENBANK/M96141
  • GENBANK/S65132
  • GENBANK/S65133