Highly Purified (~98%). The common bacterial pathogen, Staphylococcus aureus, produces a 42kD factor, protein A (SpA). The biological role of protein A is not understood fully, although it is secreted by nearly all clinical isolates of S. aureus and is thought to enhance pathogenicity. Protein A interacts with antibodies through two distinct binding events: the ``classical'' binding site on the Fc portion of human IgG1, IgG2, and IgG4, and the ``alternate'' binding site found on the Fab portion of human IgG, IgM, IgA, and IgE that contain heavy chains of the VH3 subfamily. Protein A has long been studied for its properties as a valuable immunological tool and more recently for its ability to act as a B cell superantigen by cross-linking IgM molecules through VH3- mediated binding. Protein A contains five homologous;58 residue immunoglobulin (Ig)-binding domains followed by a C-terminal region necessary for cell wall attachment. The Ig binding domains are designated E, D, A, B, and C ~in or