Removal of Mannose-Ending Glycan at Asn
Animals
Antigen Presentation
/ immunology
Dendritic Cells
/ immunology
Factor VIII
/ chemistry
Humans
Lectins, C-Type
/ immunology
Lymphocyte Activation
/ immunology
Mannose
/ chemistry
Mannose Receptor
Mannose-Binding Lectins
/ immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Monocytes
/ immunology
Mutation
Receptors, Cell Surface
/ immunology
FVIII inhibitors
N-glycosylations
factor VIII
hemophilia A
immunogenicity of therapeutic proteins
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
26
11
2019
accepted:
19
02
2020
entrez:
11
4
2020
pubmed:
11
4
2020
medline:
24
3
2021
Statut:
epublish
Résumé
The development of an immune response against therapeutic factor VIII is the major complication in hemophilia A patients. Oligomannose carbohydrates at N239 and/or N2118 on factor VIII allow its binding to the macrophage mannose receptor expressed on human dendritic cells, thereby leading to factor VIII endocytosis and presentation to CD4+ T lymphocytes. Here, we investigated whether altering the interaction of factor VIII with mannose-sensitive receptors on antigen-presenting cells may be a strategy to reduce factor VIII immunogenicity. Gene transfer experiments in factor VIII-deficient mice indicated that N239Q and/or N2118Q factor VIII mutants have similar specific activities as compared to non-mutated factor VIII; N239Q/N2118Q mutant corrected blood loss upon tail clip. Production of the corresponding recombinant FVIII mutants or light chains indicated that removal of the N-linked glycosylation site at N2118 is sufficient to abrogate
Identifiants
pubmed: 32273875
doi: 10.3389/fimmu.2020.00393
pmc: PMC7117063
doi:
Substances chimiques
Lectins, C-Type
0
Mannose Receptor
0
Mannose-Binding Lectins
0
Receptors, Cell Surface
0
Factor VIII
9001-27-8
Mannose
PHA4727WTP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
393Informations de copyright
Copyright © 2020 Delignat, Rayes, Dasgupta, Gangadharan, Denis, Christophe, Bayry, Kaveri and Lacroix-Desmazes.
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