The Moraxella catarrhalis immunoglobulin D (IgD)-binding protein (MID) is a 200-kDa outer membrane protein displaying a unique and specific affinity for human IgD. MID is found in the majority of M. catarrhalis strains. In the present paper, we show that MID-expressing M. catarrhalis strains agglutinate human erythrocytes and bind to type II alveolar epithelial cells. In contrast, M. catarrhalis isolates with low MID expression levels and two mutants deficient in MID, but with readily detectable UspA1 expression, do not agglutinate erythrocytes and have a 50% lower adhesive capacity. To examine the adhesive part of MID, the protein was dissected into nine fragments covering the entire molecule. The truncated MID proteins were expressed in Escherichia coli, purified, and used for raising polyclonal antibodies in rabbits. Interestingly, by using recombinant fragments, we show that the hemagglutinating and adhesive part of MID is localized within the 150-amino-acid fragment MID Moraxella (Branhamella) catarrhalis is often a harmless commensal in the respiratory tract and can be detected in nasopharyngeal cultures from 66% of children during the first year of life and from approximately 4% of adults at any given time. However, the species has increasingly been recognized as an important pathogen in respiratory tract infections in both children and adults (4, 15). After Haemophilus influenzae and Streptococcus pneumoniae, M. catarrhalis is the third most common bacterial agent in acute otitis media in children. In adults and the elderly, M. catarrhalis is a common cause of lower respiratory tract infections, particularly in those with predisposing conditions such as chronic obstructive pulmonary disease. M. catarrhalis is often implicated as a cause of sinusitis in both children and adults. Furthermore, the emergence of antibiotic resistance suggests that the incidence of M. catarrhalis infections may continue to rise. More than 90% of M. catarrhalis clinical isolates are resistant to penicillin, and M. catarrhalis has developed resistance at a rate unprecedented for any bacterial species. The emergence of M. catarrhalis as a significant cause of human disease has generated much interest in the identification of potential vaccine antigens (20). M. catarrhalis vaccine development is at the antigen candidate identification stage, and researchers are searching for potential vaccine antigens that elicit antibodies with capacity to limit the bacterium's pathogenicity.Two decades ago, M. catarrhalis was shown to display a strong affinity for soluble human immunoglobulin D (IgD) (9). IgD binding at the cellular level explains the strong mitogenic effects of M. catarrhalis on human lymphocytes (3, 10). In addition, it was demonstrated that M. catarrhalis stimulates the proliferation of high-density (mature) B lymphocytes expressing a high density of IgD B-cell receptors (BCR) and that soluble nonmitogenic monoclonal antibodies (MAbs) reactive with human IgD selectively inhibit the B-lymphocyte response. Inhibition by anti-Ig...