COMPLEMENTARITY-DETERMINING REGION-2 IS IMPLICATED IN THE BINDING OF STAPHYLOCOCCAL PROTEIN-A TO HUMAN-IMMUNOGLOBULIN V(H)III VARIABLE REGIONS

Staphylococcal protein A (SPA) has two distinct binding sites on human immunoglobulins. In addition to binding to the Fc region of most IgG molecules, an ''alternative'' binding site has been localized to the F ab region of human immunoglobulins encoded by heavy chain variable gen e segments belonging to the V(H)III family. Comparison of amino acid s equences of closely related SPA-binding and -non-binding proteins sugg ested that V(H)III-specific residues in the second complementarity-det ermining region (CDR2) were likely responsible for SPA binding activit y. Site-directed mutagenesis of a single amino acid residue in CDR2 co nverted an IgM rheumatoid factor which did not bind SPA to an SPA bind er. These findings, therefore, locate a critical site involved in SPA binding to the CDR2 of human immunoglobulins encoded by V(H)III family gene segments.