ENDOGENOUS SIALOPROTEIN AND A BACTERIAL B-CELL SUPERANTIGEN COMPETE IN THEIR V-H FAMILY-SPECIFIC BINDING INTERACTIONS WITH HUMAN IGS

Staphylococcal protein A (SpA), a bacterial membrane protein, and prot ein Fv (Fv binding protein (pFv)), a human sialoprotein involved in gu t-associated immunity, have both recently been shown to have unconvent ional V-H family-restricted binding interactions with Igs. To determin e whether these Ig binding proteins interact with related structures, we performed a series of comparative binding studies. The results conf irmed that both molecules are bound by most V(H)3 IgM, but pFv is also recognized by V(H)3 and V(H)G Ig that do not interact with SpA, We di scovered that pFv and SpA (or a single domain of SpA) can compete for binding to a V(H)3 Ab, which suggests that they can recognize the same (or adjacent) V-H sites. For both SpA and pFv, binding is less freque nt among Ige than IgM. However, V(H)3 IgG more commonly possess Fab-me diated binding activity for pFv than for SpA, Binding studies of denat ured Ig suggested that both pFv and SpA interact with conformationally dependent V-H sites, ao although in certain cases pFv binding is more permissive than SpA binding. Taken together, these results indicate t hat the superantigen properties of SpA, a microbial protein, and those of pFv, an endogenous sialoprotein, involve binding interactions with overlapping and at times functionally equivalent sites in the V-H dom ain, indicating that self and foreign proteins can employ highly conse rved strategies to create superantigens for the Ag receptors of B lymp hocytes.