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Clonal repertoire diversification of a neutralizing cytomegalovirus glycoprotein B-specific antibody results in variants with diverse anti-viral properties.

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Author

  • Yvelise Barrios del Pino
  • S Knör
  • Johan Lantto
  • M Mach
  • Mats Ohlin

Summary, in English

Cytomegalovirus induces a chronic infection that in normal individuals is controlled by the immune system. In the case of humoral immunity, epitopes, in particular antigenic domain-1, in glycoprotein B have proven to be important for the induction of virus-neutralizing activity. Such antibodies can exert potent virus-neutralizing activity but can also block neutralizing antibodies from binding. Furthermore, these antibodies differ in their fine recognition of antigenic domain-1 as determined by epitope mapping. By using combinatorial library and phage display technologies we have now isolated a large array of clonally related antibody fragments to understand the origin of this diversity. This procedure allowed us to demonstrate that much of the diversity in functional activity (virus neutralization) and epitope recognition can arise from a single parental molecule through somatic mutation processes. We have thus demonstrated that the clonal diversification of a single antigen-specific clone can account for much of the diversity in antibody anti-viral activity. These findings have implications on the development of a gB-based subunit vaccine, as an effective vaccine preparation need not only to recruit appropriate clones into the immune response but also to evolve them properly so as to maintain an appropriate biological function.

Publishing year

2007

Language

English

Pages

680-690

Publication/Series

Molecular Immunology

Volume

44

Issue

5

Document type

Journal article

Publisher

Pergamon Press Ltd.

Topic

  • Immunology in the medical area

Keywords

  • Antibody
  • single chain antibody fragment
  • [abr] scFv
  • polymerase chain reaction
  • [abr] PCR
  • phosphate buffered saline
  • [abr] PBS
  • light
  • heavy
  • [abr] L
  • [abr] H
  • glycoprotein B
  • [abr] gB
  • cytomegalovirus
  • [abr] CMV
  • complementarity determining region
  • [abr] CDR
  • [abr] BSA
  • bovine serum albumin
  • Cytomegalovirus
  • [abr] AD
  • Repertoire
  • Virus neutralization
  • antigenic domain
  • Phage display

Status

Published

ISBN/ISSN/Other

  • ISSN: 1872-9142