Cargando…
Human IgG4: a structural perspective
IgG4, the least represented human IgG subclass in serum, is an intriguing antibody with unique biological properties, such as the ability to undergo Fab-arm exchange and limit immune complex formation. The lack of effector functions, such as antibody-dependent cell-mediated cytotoxicity and compleme...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4670484/ https://www.ncbi.nlm.nih.gov/pubmed/26497518 http://dx.doi.org/10.1111/imr.12349 |
_version_ | 1782404262988349440 |
---|---|
author | Davies, Anna M Sutton, Brian J |
author_facet | Davies, Anna M Sutton, Brian J |
author_sort | Davies, Anna M |
collection | PubMed |
description | IgG4, the least represented human IgG subclass in serum, is an intriguing antibody with unique biological properties, such as the ability to undergo Fab-arm exchange and limit immune complex formation. The lack of effector functions, such as antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, is desirable for therapeutic purposes. IgG4 plays a protective role in allergy by acting as a blocking antibody, and inhibiting mast cell degranulation, but a deleterious role in malignant melanoma, by impeding IgG1-mediated anti-tumor immunity. These findings highlight the importance of understanding the interaction between IgG4 and Fcγ receptors. Despite a wealth of structural information for the IgG1 subclass, including complexes with Fcγ receptors, and structures for intact antibodies, high-resolution crystal structures were not reported for IgG4-Fc until recently. Here, we highlight some of the biological properties of human IgG4, and review the recent crystal structures of IgG4-Fc. We discuss the unexpected conformations adopted by functionally important Cγ2 domain loops, and speculate about potential implications for the interaction between IgG4 and FcγRs. |
format | Online Article Text |
id | pubmed-4670484 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-46704842015-12-11 Human IgG4: a structural perspective Davies, Anna M Sutton, Brian J Immunol Rev Invited Reviews IgG4, the least represented human IgG subclass in serum, is an intriguing antibody with unique biological properties, such as the ability to undergo Fab-arm exchange and limit immune complex formation. The lack of effector functions, such as antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, is desirable for therapeutic purposes. IgG4 plays a protective role in allergy by acting as a blocking antibody, and inhibiting mast cell degranulation, but a deleterious role in malignant melanoma, by impeding IgG1-mediated anti-tumor immunity. These findings highlight the importance of understanding the interaction between IgG4 and Fcγ receptors. Despite a wealth of structural information for the IgG1 subclass, including complexes with Fcγ receptors, and structures for intact antibodies, high-resolution crystal structures were not reported for IgG4-Fc until recently. Here, we highlight some of the biological properties of human IgG4, and review the recent crystal structures of IgG4-Fc. We discuss the unexpected conformations adopted by functionally important Cγ2 domain loops, and speculate about potential implications for the interaction between IgG4 and FcγRs. Blackwell Publishing Ltd 2015-11 2015-10-26 /pmc/articles/PMC4670484/ /pubmed/26497518 http://dx.doi.org/10.1111/imr.12349 Text en © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Invited Reviews Davies, Anna M Sutton, Brian J Human IgG4: a structural perspective |
title | Human IgG4: a structural perspective |
title_full | Human IgG4: a structural perspective |
title_fullStr | Human IgG4: a structural perspective |
title_full_unstemmed | Human IgG4: a structural perspective |
title_short | Human IgG4: a structural perspective |
title_sort | human igg4: a structural perspective |
topic | Invited Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4670484/ https://www.ncbi.nlm.nih.gov/pubmed/26497518 http://dx.doi.org/10.1111/imr.12349 |
work_keys_str_mv | AT daviesannam humanigg4astructuralperspective AT suttonbrianj humanigg4astructuralperspective |