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Immunoglobulin G structure and rheumatoid factor epitopes
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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6568389/ https://www.ncbi.nlm.nih.gov/pubmed/31199818 http://dx.doi.org/10.1371/journal.pone.0217624 |
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author | Maibom-Thomsen, Sheila Lefoli Trier, Nicole Hartwig Holm, Bettina Eide Hansen, Kirsten Beth Rasmussen, Morten Ib Chailyan, Anna Marcatili, Paolo Højrup, Peter Houen, Gunnar |
author_facet | Maibom-Thomsen, Sheila Lefoli Trier, Nicole Hartwig Holm, Bettina Eide Hansen, Kirsten Beth Rasmussen, Morten Ib Chailyan, Anna Marcatili, Paolo Højrup, Peter Houen, Gunnar |
author_sort | Maibom-Thomsen, Sheila Lefoli |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6568389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-65683892019-06-20 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 PLoS One Research Article 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. Public Library of Science 2019-06-14 /pmc/articles/PMC6568389/ /pubmed/31199818 http://dx.doi.org/10.1371/journal.pone.0217624 Text en © 2019 Maibom-Thomsen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article 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 |
title | Immunoglobulin G structure and rheumatoid factor epitopes |
title_full | Immunoglobulin G structure and rheumatoid factor epitopes |
title_fullStr | Immunoglobulin G structure and rheumatoid factor epitopes |
title_full_unstemmed | Immunoglobulin G structure and rheumatoid factor epitopes |
title_short | Immunoglobulin G structure and rheumatoid factor epitopes |
title_sort | immunoglobulin g structure and rheumatoid factor epitopes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6568389/ https://www.ncbi.nlm.nih.gov/pubmed/31199818 http://dx.doi.org/10.1371/journal.pone.0217624 |
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