Structure and immunological action of the human pathogen Moraxella catarrhalis IgD-binding protein

Abstract

Several pathogens have acquired the capacity to bind immunoglobulins in a nonimmune manner, that is, the binding does not involve the normal antigen-binding sites of the antibodies. In contrast to gram-positive bacteria, for example Staphylococus aureus, nonimmune binding to gram-negative bacteria is rare. Moraxella catarrhalis outer membrane protein MID is the first to date known IgD-binding protein. MID is a 200-kDa autotransporter protein that exists as an oligomer and is governed at the transcriptional level. The majority of M. catarrhalis clinical isolates expresses MID. Two functional domains have been attributed to MID. MID764-913 functions as an adhesin and promotes the bacteria to attach to epithelial cells. The IgD-binding domain is located within MID962-1200 and the IgD-binding is related to the secondary and tertiary structure, that is, an oligomer is required for an optimal interaction. In parallel, M. catarrhalis activates B lymphocytes through the IgD B-cell receptor. This stimulatory capacity can be blocked by anti-IgD polyclonal antibodies, and M. catarrhalis mutants devoid of MID do not stimulate B cells. Moreover, MID and MID962-1200 activates B lymphocytes in the presence of T-helper 2 cytokines or soluble CD40L. Thus, available data suggest that MID is a T-cell-independent antigen.