Removal of Mannose-Ending Glycan at Asn²¹¹⁸ Abrogates FVIII Presentation by Human Monocyte-Derived Dendritic Cells.

ABSTRACT: 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 t

SUBMITTER: Delignat S 

PROVIDER: S-EPMC7117063 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature