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Effector Functions of Camelid Heavy-Chain Antibodies in Immunity to West Nile Virus

Effector Functions of Camelid Heavy-Chain Antibodies in Immunity to West Nile Virus Three classes of IgG have been described for camelids. IgG1 has a conventional four-chain structure, while IgG2 and IgG3 do not incorporate light chains. The structures and antigen-binding affinities of the so-called heavy-chain classes have been studied in detail; however, their regulation and effector functions are largely undefined. The aim of this study was to examine the participation of conventional and heavy-chain IgG antibodies in the camelid immune defense directed against West Nile virus (WNV). We found that natural infection or vaccination with killed WNV induced IgG1 and IgG3. Vaccination also induced IgG1 and IgG3; IgG2 was produced during the anamnestic response to vaccination. When purified IgGs were tested in plaque-reduction neutralization titer (PRNT) tests, IgG3 demonstrated PRNT activities comparable to those of conventional IgG1. In contrast, IgG2 demonstrated only suboptimal activity at the highest concentrations tested. Flow cytometric analysis revealed that macrophages bound IgG1, IgG2, and IgG3. Furthermore, subneutralizing concentrations of all three isotypes enhanced WNV infection of cultured macrophages. Our results document distinctions in regulation and function between camelid heavy-chain isotypes. The reduced size and distinct structure of IgG3 did not negatively impact its capacity to neutralize virus. In contrast, IgG2 appeared to be less efficient in neutralization. This information advances our understanding of these unusual antibodies in ways that can be applied in the development of effective vaccines for camelids. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical and Vaccine Immunology American Society For Microbiology

Effector Functions of Camelid Heavy-Chain Antibodies in Immunity to West Nile Virus

Effector Functions of Camelid Heavy-Chain Antibodies in Immunity to West Nile Virus

Clinical and Vaccine Immunology , Volume 17 (2): 239 – Feb 1, 2010

Abstract

Three classes of IgG have been described for camelids. IgG1 has a conventional four-chain structure, while IgG2 and IgG3 do not incorporate light chains. The structures and antigen-binding affinities of the so-called heavy-chain classes have been studied in detail; however, their regulation and effector functions are largely undefined. The aim of this study was to examine the participation of conventional and heavy-chain IgG antibodies in the camelid immune defense directed against West Nile virus (WNV). We found that natural infection or vaccination with killed WNV induced IgG1 and IgG3. Vaccination also induced IgG1 and IgG3; IgG2 was produced during the anamnestic response to vaccination. When purified IgGs were tested in plaque-reduction neutralization titer (PRNT) tests, IgG3 demonstrated PRNT activities comparable to those of conventional IgG1. In contrast, IgG2 demonstrated only suboptimal activity at the highest concentrations tested. Flow cytometric analysis revealed that macrophages bound IgG1, IgG2, and IgG3. Furthermore, subneutralizing concentrations of all three isotypes enhanced WNV infection of cultured macrophages. Our results document distinctions in regulation and function between camelid heavy-chain isotypes. The reduced size and distinct structure of IgG3 did not negatively impact its capacity to neutralize virus. In contrast, IgG2 appeared to be less efficient in neutralization. This information advances our understanding of these unusual antibodies in ways that can be applied in the development of effective vaccines for camelids.

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References (36)

Publisher
American Society For Microbiology
Copyright
Copyright © 2010 by the American Society For Microbiology.
ISSN
1556-6811
eISSN
1556-6811
DOI
10.1128/CVI.00421-09
Publisher site
See Article on Publisher Site

Abstract

Three classes of IgG have been described for camelids. IgG1 has a conventional four-chain structure, while IgG2 and IgG3 do not incorporate light chains. The structures and antigen-binding affinities of the so-called heavy-chain classes have been studied in detail; however, their regulation and effector functions are largely undefined. The aim of this study was to examine the participation of conventional and heavy-chain IgG antibodies in the camelid immune defense directed against West Nile virus (WNV). We found that natural infection or vaccination with killed WNV induced IgG1 and IgG3. Vaccination also induced IgG1 and IgG3; IgG2 was produced during the anamnestic response to vaccination. When purified IgGs were tested in plaque-reduction neutralization titer (PRNT) tests, IgG3 demonstrated PRNT activities comparable to those of conventional IgG1. In contrast, IgG2 demonstrated only suboptimal activity at the highest concentrations tested. Flow cytometric analysis revealed that macrophages bound IgG1, IgG2, and IgG3. Furthermore, subneutralizing concentrations of all three isotypes enhanced WNV infection of cultured macrophages. Our results document distinctions in regulation and function between camelid heavy-chain isotypes. The reduced size and distinct structure of IgG3 did not negatively impact its capacity to neutralize virus. In contrast, IgG2 appeared to be less efficient in neutralization. This information advances our understanding of these unusual antibodies in ways that can be applied in the development of effective vaccines for camelids.

Journal

Clinical and Vaccine ImmunologyAmerican Society For Microbiology

Published: Feb 1, 2010

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