Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the V4-21 gene segment Academic Article Article uri icon

Overview

MeSH Major

  • Esophageal Perforation
  • Intestinal Perforation
  • Stomach Diseases

abstract

  • The anti-idiotypic (anti-Id) antibody (Ab) 9G4 binds a cross-reactive idiotope (CRI) present in a select group of human autoantibodies. This Id has been localized to the portion of immunoglobulin (Ig) heavy (H) chains encoded by the VH4-21 gene segment, a member of the human VH4 family. This gene segment is utilized by essentially all cold agglutinin (CA) Abs with I/i specificity isolated from patients with CA disease stemming from chronic lymphoproliferative disorders. In this study, mutational analysis of a CA has been used to determine the structural basis for 9G4 binding to Abs utilizing the VH4-21 gene segment. Recombinant CA H chain mutants were produced and their 9G4 reactivity determined. Mutants were generated by exchanging VH4-21 sequences in the FR1, CDR1, and CDR2 with corresponding sequences from a closely related gene segment V71-2, a VH4 family member that is associated neither with Abs having CA activity nor with Abs that react with 9G4. The results indicate that the motif AVY at amino acid positions 23-25 in FR1 defines the 9G4 idiotope. Reaction of these recombinant Abs with a polyclonal rabbit anti-CA antiserum absorbed to render it specific for a CA CRI also maps predominantly to FR1. These findings indicate that the solvent-exposed FR1 plays an important role in eliciting an immune response to Igs.

publication date

  • October 1993

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1084/jem.178.4.1419

PubMed ID

  • 8376944

Additional Document Info

start page

  • 1419

end page

  • 28

volume

  • 178

number

  • 4