Human IgA and IgG F(ab')2 that bind to staphylococcal protein A belong to the VHIII subgroup.
Staphylococcal protein A (SPA) is a bacterial membrane protein that possesses, in addition to its Fc gamma-binding activity, a distinct specificity for the Fab region of some IgM, IgA, IgG, and IgE. The Fab site that binds to SPA has been localized to the V region of the Ig H chain. In a previous study of human monoclonal and polyclonal IgM, we demonstrated that binding to SPA was highly restricted to molecules of the VHIII subgroup, and that nearly all VHIII IgM were able to bind SPA. The present study examines the VH composition of SPA-binding and SPA-nonbinding fractions of purified human polyclonal IgA, and IgG F(ab')2 fragments. We found that 22% of the IgA and 15% of the IgG F(ab')2 bound to SPA-agarose. Analysis with VH subgroup-specific antisera indicated that the SPA-binding fraction of IgA was dominated by the VHIII subgroup, and the SPA-binding fraction of IgG F(ab')2 contained only VHIII molecules. Furthermore, substantial portions of the total VHIII protein in IgA and in IgG F(ab')2 bound to SPA. We conclude that Fab binding to SPA is both restricted to and highly prevalent among human VHIII molecules, regardless of Ig class. These results suggest that protein A is an Ig superantigen.
Sasso
E H
EH
Department of Medicine, University of Washington, Seattle 98195.
Silverman
G J
GJ
Mannik
M
M
D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D015153:Blotting, Western; D006801:Humans; D007070:Immunoglobulin A / Q000145:classification* / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000145:classification* / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000378:metabolism; D066298:In Vitro Techniques; D013205:Staphylococcal Protein A / Q000276:immunology*
D007070:Immunoglobulin A; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D013205:Staphylococcal Protein A