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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0217624 |
| _version_ | 1819115121255907328 |
|---|---|
| author | Sheila Lefoli Maibom-Thomsen Nicole Hartwig Trier Bettina Eide Holm Kirsten Beth Hansen Morten Ib Rasmussen Anna Chailyan Paolo Marcatili Peter Højrup Gunnar Houen |
| author_facet | Sheila Lefoli Maibom-Thomsen Nicole Hartwig Trier Bettina Eide Holm Kirsten Beth Hansen Morten Ib Rasmussen Anna Chailyan Paolo Marcatili Peter Højrup Gunnar Houen |
| author_sort | Sheila Lefoli Maibom-Thomsen |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T04:56:09Z |
| format | Article |
| id | doaj.art-8182c74571d94b359ea6c0e65d38cc51 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T04:56:09Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8182c74571d94b359ea6c0e65d38cc512022-12-21T18:38:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01146e021762410.1371/journal.pone.0217624Immunoglobulin G structure and rheumatoid factor epitopes.Sheila Lefoli Maibom-ThomsenNicole Hartwig TrierBettina Eide HolmKirsten Beth HansenMorten Ib RasmussenAnna ChailyanPaolo MarcatiliPeter HøjrupGunnar HouenAntibodies 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.https://doi.org/10.1371/journal.pone.0217624 |
| spellingShingle | Sheila Lefoli Maibom-Thomsen Nicole Hartwig Trier Bettina Eide Holm Kirsten Beth Hansen Morten Ib Rasmussen Anna Chailyan Paolo Marcatili Peter Højrup Gunnar Houen Immunoglobulin G structure and rheumatoid factor epitopes. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0217624 |
| work_keys_str_mv | AT sheilalefolimaibomthomsen immunoglobulingstructureandrheumatoidfactorepitopes AT nicolehartwigtrier immunoglobulingstructureandrheumatoidfactorepitopes AT bettinaeideholm immunoglobulingstructureandrheumatoidfactorepitopes AT kirstenbethhansen immunoglobulingstructureandrheumatoidfactorepitopes AT mortenibrasmussen immunoglobulingstructureandrheumatoidfactorepitopes AT annachailyan immunoglobulingstructureandrheumatoidfactorepitopes AT paolomarcatili immunoglobulingstructureandrheumatoidfactorepitopes AT peterhøjrup immunoglobulingstructureandrheumatoidfactorepitopes AT gunnarhouen immunoglobulingstructureandrheumatoidfactorepitopes |