Aglycosylated immunoglobulin G^sub 1^ variants productively engage activating Fc receptors
Immunoglobulin G plays a vital role in adaptive immunity and antibody-based therapy through engagement of its Fc region by the Fc... receptors (Fc...Rs) on immune cells. In addition to specific protein-protein contacts, N-linked glycosylation of the IgG Fc has been thought to be essential for the re...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2008-12, Vol.105 (51), p.20167 |
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| container_issue | 51 |
| container_start_page | 20167 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 105 |
| creator | Sazinsky, Stephen L Ott, René G Silver, Nathaniel W Tidor, Bruce Ravetch, Jeffrey V Wittrup, K Dane |
| description | Immunoglobulin G plays a vital role in adaptive immunity and antibody-based therapy through engagement of its Fc region by the Fc... receptors (Fc...Rs) on immune cells. In addition to specific protein-protein contacts, N-linked glycosylation of the IgG Fc has been thought to be essential for the recognition of Fc by Fc...R. This requirement for the N-linked glycan has limited biomanufacture of therapeutic antibodies by restricting it to mammalian expression systems. We report here aglycosylated Fc domain variants that maintain engagement to Fc...Rs, both in vitro and in vivo, demonstrating that Fc glycosylation is not strictly required for the activation of immune cells by IgG. These variants provide insight into how the N-linked glycan is used biologically in the recognition of Fc by Fc...Rs, as well as represent a step toward the production in alternative expression systems of antibody-based therapeutics capable of eliciting immune effector functions. (ProQuest: ... denotes formulae/symbols omitted.) |
| format | Article |
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In addition to specific protein-protein contacts, N-linked glycosylation of the IgG Fc has been thought to be essential for the recognition of Fc by Fc...R. This requirement for the N-linked glycan has limited biomanufacture of therapeutic antibodies by restricting it to mammalian expression systems. We report here aglycosylated Fc domain variants that maintain engagement to Fc...Rs, both in vitro and in vivo, demonstrating that Fc glycosylation is not strictly required for the activation of immune cells by IgG. These variants provide insight into how the N-linked glycan is used biologically in the recognition of Fc by Fc...Rs, as well as represent a step toward the production in alternative expression systems of antibody-based therapeutics capable of eliciting immune effector functions. 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| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2008-12, Vol.105 (51), p.20167 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_proquest_journals_201394097 |
| source | JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Biochemistry Glycosylation Immune system Immunoglobulins Immunology Proteins |
| title | Aglycosylated immunoglobulin G^sub 1^ variants productively engage activating Fc receptors |
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