Human Antibody Responses to Bacterial Antigens: Studies of a Model Conventional Antigen and a Proposed Model B Cell Superantigen

Abstract

We have investigated the human antibody repertoires that bind to two different classes of bacterial antigens. Immunization with the conventional antigen, type b capsular polysaccharide of Haemophilus influenzae Hib PS, uniformly induces IgA and IgG responses dominated by clones that use heavy chains structurally related to two subsets of V_H³ genes, while in a minority of subjects antibodies from the V_H1 or V_H4 families are co-induced. In contrast, the “alternative binding site” of Staphylococcal Protein A (SPA) represents an unconventional determinant, because; (i) SPA is bound by a large proportion of non-immune IgM, IgA and IgG F(ab')², (ii) SPA is bound only to Fab from the V_H3 family, which can be encoded by at least four different germline genes, (iii) SPA binding is independent of V_L usage, (iv) by flow cytometry SPA is bound by > 15% of tonsilar B cells, but not to T cells, (v) In vitro stimulation with an SPA containing mitogen induces the preferentially production of Ig bearing a V_H3 marker. Taken together, these studies characterize a V_H family restricted binding interaction that is distinct from the properties associated with conventional antigens such as Hib PS. Based on these data we propose that SPA represents a prototype for a B cell superantigen.

Key Words:

• repertoire
• superantigen
• protein A
• Haemophilus influenzae
• antibody
• variable region