The WI-1 antigen of Blastomyces dermatitidis yeasts mediates binding to human macrophage CD11b/CD18 (CR3) and CD14.
Three genetically related strains of Blastomyces dermatitidis (Bd) yeasts that differ in their expression of WI-1, an immunodominant cell wall Ag, were tested for their capacity to bind to human macrophages (M phi) in the absence of serum. These strains included American Type Culture Collection (ATCC, Rockville, MD) ATCC 26199, which is virulent for mice; an attenuated mutant strain ATCC 60915, which expresses 2.5-fold more WI-1 than strain 26199; and an avirulent mutant strain, ATCC 60916, which has sixfold more WI-1 than strain 26199. Attachment of both mutant strains to M phi was rapid and was maximum after 10 min at 37 degrees C. Attachment of strain 26199 to M phi was approximately 40% of that obtained with the mutants. Binding of Bd to M phi was temperature- and Mg(2+)-dependent, and heat-killed yeasts bound to M phi as well as viable yeasts. Experiments with receptor-specific mAbs demonstrated that 26199 yeasts bound predominantly to the LPS binding site on CD11b/CD18 (CR3). However, the mutants bound to M phi CD14 as well as CR3. Fab anti-WI-1 inhibited the binding of all strains to M phi by 69 to 78%. Latex microspheres coated with purified WI-1 or a 25-amino acid tandem repeat located within WI-1 also bound to M phi CR3 and CD14. These data demonstrate that: 1) WI-1 is a major ligand on Bd that mediates attachment of yeasts to human M phi; 2) the binding activity of WI-1 is located within the 25-amino acid tandem repeat; and 3) binding of Bd yeasts to M phi is mediated through the LPS binding site on CR3 and CD14.
Newman
S L
SL
Department of Medicine, University of Cincinnati College of Medicine, OH 45267.
Chaturvedi
S
S
Klein
B S
BS
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000946:Antigens, Fungal / Q000737:chemistry / Q000276:immunology*; D001758:Blastomyces / Q000276:immunology*; D002413:Cations, Divalent; D002448:Cell Adhesion / Q000276:immunology; D005434:Flow Cytometry; D005656:Fungal Proteins; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D018950:Lipopolysaccharide Receptors; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D008863:Microspheres
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000946:Antigens, Fungal; D002413:Cations, Divalent; D005656:Fungal Proteins; D006023:Glycoproteins; D018950:Lipopolysaccharide Receptors; D016177:Macrophage-1 Antigen