Immunoglobulin G structure and rheumatoid factor epitopes

Sheila Lefoli Maibom-Thomsen, Nicole Hartwig Trier, Bettina Eide Holm, Kirsten Beth Hansen, Morten Ib Rasmussen, Anna Chailyan, Paolo Marcatili, Peter Højrup, Gunnar Houen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

107 Downloads (Pure)

Abstract

Antibodies are important for immunity and exist in several classes (IgM, IgD, IgA, IgG, IgE). They are composed of symmetric dimeric molecules with two antigen binding regions (Fab) and a constant part (Fc), usually depicted as Y-shaped molecules. Rheumatoid factors found in patients with rheumatoid arthritis are autoantibodies binding to IgG and paradoxically appear to circulate in blood alongside with their antigen (IgG) without reacting with it. Here, it is shown that rheumatoid factors do not react with native IgG in solution, and that their epitopes only become accessible upon certain physico-chemical treatments (e.g. heat treatment at 57 °C), by physical adsorption on a hydrophobic surface or by antigen binding. Moreover, chemical cross-linking in combination with mass spectrometry showed that the native state of IgG is a compact (closed) form and that the Fab parts of IgG shield the Fc region and thereby control access of rheumatoid factors and presumably also some effector functions. It can be inferred that antibody binding to pathogen surfaces induces a conformational change, which exposes the Fc part with its effector sites and rheumatoid factor epitopes. This has strong implications for understanding antibody structure and physiology and necessitates a conceptual reformulation of IgG models.

Original languageEnglish
Article numbere0217624
JournalPLOS ONE
Volume14
Issue number6
Number of pages28
ISSN1932-6203
DOIs
Publication statusPublished - 14. Jun 2019

Fingerprint

Rheumatoid Factor
immunoglobulin G
epitopes
Epitopes
Immunoglobulin G
antigens
antibodies
autoantibodies
rheumatoid arthritis
chemical treatment
crosslinking
Antigens
adsorption
physiology
immunity
Antibodies
heat treatment
mass spectrometry
pathogens
Immunoglobulin D

Cite this

Maibom-Thomsen, S. L., Trier, N. H., Holm, B. E., Hansen, K. B., Rasmussen, M. I., Chailyan, A., ... Houen, G. (2019). Immunoglobulin G structure and rheumatoid factor epitopes. PLOS ONE, 14(6), [e0217624]. https://doi.org/10.1371/journal.pone.0217624
Maibom-Thomsen, Sheila Lefoli ; Trier, Nicole Hartwig ; Holm, Bettina Eide ; Hansen, Kirsten Beth ; Rasmussen, Morten Ib ; Chailyan, Anna ; Marcatili, Paolo ; Højrup, Peter ; Houen, Gunnar. / Immunoglobulin G structure and rheumatoid factor epitopes. In: PLOS ONE. 2019 ; Vol. 14, No. 6.
@article{5460ac79c8b44d038a284a1371a21a10,
title = "Immunoglobulin G structure and rheumatoid factor epitopes",
abstract = "Antibodies are important for immunity and exist in several classes (IgM, IgD, IgA, IgG, IgE). They are composed of symmetric dimeric molecules with two antigen binding regions (Fab) and a constant part (Fc), usually depicted as Y-shaped molecules. Rheumatoid factors found in patients with rheumatoid arthritis are autoantibodies binding to IgG and paradoxically appear to circulate in blood alongside with their antigen (IgG) without reacting with it. Here, it is shown that rheumatoid factors do not react with native IgG in solution, and that their epitopes only become accessible upon certain physico-chemical treatments (e.g. heat treatment at 57 °C), by physical adsorption on a hydrophobic surface or by antigen binding. Moreover, chemical cross-linking in combination with mass spectrometry showed that the native state of IgG is a compact (closed) form and that the Fab parts of IgG shield the Fc region and thereby control access of rheumatoid factors and presumably also some effector functions. It can be inferred that antibody binding to pathogen surfaces induces a conformational change, which exposes the Fc part with its effector sites and rheumatoid factor epitopes. This has strong implications for understanding antibody structure and physiology and necessitates a conceptual reformulation of IgG models.",
author = "Maibom-Thomsen, {Sheila Lefoli} and Trier, {Nicole Hartwig} and Holm, {Bettina Eide} and Hansen, {Kirsten Beth} and Rasmussen, {Morten Ib} and Anna Chailyan and Paolo Marcatili and Peter H{\o}jrup and Gunnar Houen",
year = "2019",
month = "6",
day = "14",
doi = "10.1371/journal.pone.0217624",
language = "English",
volume = "14",
journal = "P L o S One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

Maibom-Thomsen, SL, Trier, NH, Holm, BE, Hansen, KB, Rasmussen, MI, Chailyan, A, Marcatili, P, Højrup, P & Houen, G 2019, 'Immunoglobulin G structure and rheumatoid factor epitopes', PLOS ONE, vol. 14, no. 6, e0217624. https://doi.org/10.1371/journal.pone.0217624

Immunoglobulin G structure and rheumatoid factor epitopes. / Maibom-Thomsen, Sheila Lefoli; Trier, Nicole Hartwig; Holm, Bettina Eide; Hansen, Kirsten Beth; Rasmussen, Morten Ib; Chailyan, Anna; Marcatili, Paolo; Højrup, Peter; Houen, Gunnar.

In: PLOS ONE, Vol. 14, No. 6, e0217624, 14.06.2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Immunoglobulin G structure and rheumatoid factor epitopes

AU - Maibom-Thomsen, Sheila Lefoli

AU - Trier, Nicole Hartwig

AU - Holm, Bettina Eide

AU - Hansen, Kirsten Beth

AU - Rasmussen, Morten Ib

AU - Chailyan, Anna

AU - Marcatili, Paolo

AU - Højrup, Peter

AU - Houen, Gunnar

PY - 2019/6/14

Y1 - 2019/6/14

N2 - Antibodies are important for immunity and exist in several classes (IgM, IgD, IgA, IgG, IgE). They are composed of symmetric dimeric molecules with two antigen binding regions (Fab) and a constant part (Fc), usually depicted as Y-shaped molecules. Rheumatoid factors found in patients with rheumatoid arthritis are autoantibodies binding to IgG and paradoxically appear to circulate in blood alongside with their antigen (IgG) without reacting with it. Here, it is shown that rheumatoid factors do not react with native IgG in solution, and that their epitopes only become accessible upon certain physico-chemical treatments (e.g. heat treatment at 57 °C), by physical adsorption on a hydrophobic surface or by antigen binding. Moreover, chemical cross-linking in combination with mass spectrometry showed that the native state of IgG is a compact (closed) form and that the Fab parts of IgG shield the Fc region and thereby control access of rheumatoid factors and presumably also some effector functions. It can be inferred that antibody binding to pathogen surfaces induces a conformational change, which exposes the Fc part with its effector sites and rheumatoid factor epitopes. This has strong implications for understanding antibody structure and physiology and necessitates a conceptual reformulation of IgG models.

AB - Antibodies are important for immunity and exist in several classes (IgM, IgD, IgA, IgG, IgE). They are composed of symmetric dimeric molecules with two antigen binding regions (Fab) and a constant part (Fc), usually depicted as Y-shaped molecules. Rheumatoid factors found in patients with rheumatoid arthritis are autoantibodies binding to IgG and paradoxically appear to circulate in blood alongside with their antigen (IgG) without reacting with it. Here, it is shown that rheumatoid factors do not react with native IgG in solution, and that their epitopes only become accessible upon certain physico-chemical treatments (e.g. heat treatment at 57 °C), by physical adsorption on a hydrophobic surface or by antigen binding. Moreover, chemical cross-linking in combination with mass spectrometry showed that the native state of IgG is a compact (closed) form and that the Fab parts of IgG shield the Fc region and thereby control access of rheumatoid factors and presumably also some effector functions. It can be inferred that antibody binding to pathogen surfaces induces a conformational change, which exposes the Fc part with its effector sites and rheumatoid factor epitopes. This has strong implications for understanding antibody structure and physiology and necessitates a conceptual reformulation of IgG models.

U2 - 10.1371/journal.pone.0217624

DO - 10.1371/journal.pone.0217624

M3 - Journal article

C2 - 31199818

AN - SCOPUS:85067487951

VL - 14

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 6

M1 - e0217624

ER -

Maibom-Thomsen SL, Trier NH, Holm BE, Hansen KB, Rasmussen MI, Chailyan A et al. Immunoglobulin G structure and rheumatoid factor epitopes. PLOS ONE. 2019 Jun 14;14(6). e0217624. https://doi.org/10.1371/journal.pone.0217624