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

Barrios del Pino, Yvelise LU ; Knör, S; Lantto, Johan LU ; Mach, M and Ohlin, Mats LU (2007) In Molecular Immunology 44(5). p.680-690
Abstract
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... (More)
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. (Less)
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organization
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Contribution to journal
publication status
published
subject
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
in
Molecular Immunology
volume
44
issue
5
pages
680 - 690
publisher
Pergamon
external identifiers
  • WOS:000242020100002
  • Scopus:33748781701
ISSN
1872-9142
DOI
10.1016/j.molimm.2006.04.024
language
English
LU publication?
yes
id
99509438-4cde-466e-ad8b-ccd3012860cd (old id 594465)
date added to LUP
2007-11-27 15:52:37
date last changed
2016-10-13 04:26:01
@misc{99509438-4cde-466e-ad8b-ccd3012860cd,
  abstract     = {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.},
  author       = {Barrios del Pino, Yvelise and Knör, S and Lantto, Johan and Mach, M and Ohlin, Mats},
  issn         = {1872-9142},
  keyword      = {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},
  language     = {eng},
  number       = {5},
  pages        = {680--690},
  publisher    = {ARRAY(0x9a9ae20)},
  series       = {Molecular Immunology},
  title        = {Clonal repertoire diversification of a neutralizing cytomegalovirus glycoprotein B-specific antibody results in variants with diverse anti-viral properties.},
  url          = {http://dx.doi.org/10.1016/j.molimm.2006.04.024},
  volume       = {44},
  year         = {2007},
}