Two separate non-immune interactions between staphylococcal protein A and immunoglobulins are mediated by structures on gamma chains.

The present investigation was undertaken to determine whether the light or the heavy immunoglobulin chain is involved in the alternative, non-immune F(ab')2-mediated binding to staphylococcal protein A. Purified human polyclonal IgG was mildly reduced with dithiothreitol and alkylated with iodoacetamide. Intact IgG, purified light and heavy chains of polyclonal immunoglobulin G were tested in an inhibition assay for alternative non-immune F(ab')2-mediated binding to the protein A-carrying S. aureus, strain Cowan I. The IgG Fc-mediated binding to protein A was studied in parallel inhibition experiments. Heavy chains inhibited both the alternative F(ab')2- and the classical Fc-mediated binding to protein A. Isolated light chains were non-reactive. Intact IgG molecules were more potent inhibitors than isolated heavy chains tested in equimolar concentrations. Our results indicate that the alternative non-immune interaction between staphylococcal protein A and human immunoglobulins is mediated by structures expressed on the heavy immunoglobulin G chain. Thus, there are two separate protein A binding sites on gamma chains.