Monoclonal antibodies can affect complement deposition on the capsule of the pathogenic fungus Cryptococcus neoformans by both classical pathway activation and steric hindrance.
The capsule of the human pathogenic fungus Cryptococcus neoformans presents the immune system with a formidable problem for phagocytosis. Capsule-mediated activation of the alternative complement (C) pathway results in component 3 (particularly, C3) binding to the capsule near the cell wall surface. Hence, for cells with large capsule, C3 cannot interact with the complement receptor (CR) and is not opsonic. However, C activation in either immune serum or in the presence of monoclonal antibody (mAb) to capsular polysaccharide localizes C3 to the capsular edge. When C. neoformans cells were coated with both C and antibody (Ab) opsonins, Ab bound first and promoted C3 deposition at the edge of the capsule. The mechanism for the Ab-mediated change in C3 localization to the capsule edge involved both classical C pathway activation and steric hindrance preventing C3 penetration into the capsule. The change in C3 localization changed the mode of phagocytosis in macrophages, such that localizing C3 at the edge of the capsule allowed phagocytosis through C3-CR3 and C3-CR4 interactions, which did not occur in serum without Ab. These findings reveal a new mechanism of Ab action whereby Abs affect the location of C3 and its interaction with its receptor in macrophages depending on the immunoglobulin concentration.
Zaragoza
Oscar
O
Albert Einstein College of Medicine, Departments of Microbiology and Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Casadevall
Arturo
A
D000908:Antibodies, Fungal / Q000737:chemistry / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D000946:Antigens, Fungal / Q000276:immunology; D001666:Binding Sites, Antibody; D003176:Complement C3 / Q000032:analysis / Q000378:metabolism*; D003171:Complement Pathway, Classical; D003453:Cryptococcosis / Q000276:immunology*; D003455:Cryptococcus neoformans / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D006801:Humans; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis
D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal; D003176:Complement C3; D009895:Opsonin Proteins