Influence of IgG subclass on human antimannan antibody-mediated resistance to hematogenously disseminated candidiasis in XXXX .

@entity1 @entity6923 @entity19 @entity9686 @entity5132 @entity375
UNASSIGNED: @entity5132 is a @entity375 -like pathogen and can cause life-threatening @entity6923 . Its cell surface is enriched with mannan that is resistant to complement activation. Previously, we developed the recombinant human @entity9686 antimannan antibody M1g1. M1g1 was found to promote complement activation and phagocytosis and protect @entity19 from @entity6923 . Here, we evaluate the influence of IgG subclass on antimannan antibody-mediated protection. Three IgG subclass variants of M1g1 were constructed: M1g2, M1g3, and M1g4. The IgG subclass identity for each of the four variants was confirmed with DNA sequence and subclass-specific antibodies. These variants contain the identical M1 Fab and exhibited similar binding affinities for @entity5132 @entity375 and purified mannan. @entity375 cells and hyphae recovered from the kidney of antibody-treated @entity19 with @entity6923 showed uniform binding of each variant, indicating constitutive expression of the M1 epitope and antibody opsonization in the kidney. All variants promoted deposition of both @entity19 and @entity1 C3 onto the @entity375 cell surface with M1g4 showing a delayed activation, as determined by flow cytometry and immunofluorescence microscopy. M1g4-mediated complement activation was found to be associated with its M1 Fab that activates the alternative pathway in an Fc-independent manner. Treatment with each subclass variant extended the survival of @entity19 with @entity6923 (P < 0.001). However, except M1g2, treatment with M1g1, M1g3 or M1g4 also reduced the kidney fungal burden (P < 0.001). Thus, the role of human antimannan antibody in host resistance to @entity6923 is influenced by its IgG subclass.
