Variable region identical immunoglobulins differing in isotype express different paratopes

Alena Janda, Ertan Eryilmaz, Antonio Nakouzi, David Cowburn, Arturo Casadevall

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The finding that the antibody (Ab) constant (C) region can influence fine specificity suggests that isotype switching contributes to the generation of Ab diversity and idiotype restriction. Despite the centrality of this observation for diverse immunological effects such as vaccine responses, isotype-restricted antibody responses, and the origin of primary and secondary responses, the molecular mechanism(s) responsible for this phenomenon are not understood. In this study, we have taken a novel approach to the problem by probing the paratope with 15N label peptide mimetics followed by NMR spectroscopy and fluorescence emission spectroscopy. Specifically, we have explored the hypothesis that the C region imposes conformational constraints on the variable (V) region to affect paratope structure in a V region identical IgG1, IgG2a, IgG2b, and IgG3 mAbs. The results reveal isotype-related differences in fluorescence emission spectroscopy and temperature-related differences in binding and cleavage of a peptide mimetic. We conclude that the C region can modify the V region structure to alter the Ab paratope, thus providing an explanation for how isotype can affect Ab specificity.

Original languageEnglish (US)
Pages (from-to)35409-35417
Number of pages9
JournalJournal of Biological Chemistry
Volume287
Issue number42
DOIs
StatePublished - Oct 12 2012

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Immunoglobulin Variable Region
Antibody Binding Sites
Fluorescence Spectrometry
Antibodies
Antibody Diversity
Immunoglobulin G
Immunoglobulin Class Switching
Fluorescence spectroscopy
Emission spectroscopy
Peptides
Antibody Specificity
Antibody Formation
Magnetic Resonance Spectroscopy
Vaccines
Temperature
Nuclear magnetic resonance spectroscopy
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ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Variable region identical immunoglobulins differing in isotype express different paratopes. / Janda, Alena; Eryilmaz, Ertan; Nakouzi, Antonio; Cowburn, David; Casadevall, Arturo.

In: Journal of Biological Chemistry, Vol. 287, No. 42, 12.10.2012, p. 35409-35417.

Research output: Contribution to journalArticle

Janda, Alena ; Eryilmaz, Ertan ; Nakouzi, Antonio ; Cowburn, David ; Casadevall, Arturo. / Variable region identical immunoglobulins differing in isotype express different paratopes. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 42. pp. 35409-35417.
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