Fcγ-like Determinants on Immunoglobulin Variable Regions: Identification by Staphylococcal Protein A.

Protein A from Staphylococcus aureus is widely known as a ligand specific for the Fc portion of the IgG molecule. However, recent reports suggest that a minor proportion of immunoglobulins may also carry protein-A-reactive sites in their Fab portion. I found that about 5% of polyclonal Fabγ and Fabα fragments strongly bound protein A. Moreover, 2 of 18 human IgG myelomas showed a similar reactivity. This interaction was not due to a conventional anti-protein-A antibody activity, since it was possible to obtain F(ab')₂, from human IgG anti-tetanus toxoid, and Fab, from mouse IgG anti-sheep erythrocytes, which were able to bind protein A and the immunogen. The finding that a proportion of Fv fragments (V_H + V_L domain), obtained from normal human IgM, also interacts with protein A suggests that the reactive site is located within the framework of the variable portion of a subset of immunoglobins. The ability of these F(ab')₂ fragments to inhibit efficiently the binding of [¹²⁵I]protein. A to immobolized human Fcγ fragments, suggests that these immunoglobulins express, within their variable regions, determinants that possess Fcγ-like properties. [ABSTRACT FROM AUTHOR]