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

Författare:
  • Yvelise Barrios del Pino
  • S Knör
  • Johan Lantto
  • M Mach
  • Mats Ohlin
Publiceringsår: 2007
Språk: Engelska
Sidor: 680-690
Publikation/Tidskrift/Serie: Molecular Immunology
Volym: 44
Nummer: 5
Dokumenttyp: Artikel

Sammanfattning

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.

Disputation

Nyckelord

  • Biology and Life Sciences
  • 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

Övriga

Published
Yes
  • ISSN: 0161-5890

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