IGG SUBCLASS RESPONSE TO A ACTINOMYCETEMCOMITANS

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Localized juvenile periodontitis (LJP) subjects colonized by the gram-negative coccobacillus Actinobacillus actinomycetemcomitans frequently exhibit markedly elevated serum IgG antibody titers to this organism. Recent studies have demonstrated that the humoral response of LJP subjects includes production of specific IgG antibodies directed toward outer membrane proteins and lipopolysaccharide present in the outer membrane of this organism. However, the significance of the antibody response to A. actinomycetemcomitans surface antigens is incompletely understood. It has been appreciated for some years that human serum IgG consists of four distinct subclasses. These four subclasses differ not only in their biologic properties (particularly with respect to complement activation and binding to phagocyte Fc receptors), but in the nature of the antigens which induce their production. Only IgG subclasses (IgG1 and IgG3) which activate complement and interact well with Fc receptors on phagocytic cells tend to promote bacterial opsonization and phagocytic killing. In general, protein antigens preferentially induce IgG1, whereas polysaccharide antigens induce mainly IgG2. The predominant IgG subclass response to bacterial infection can significantly influence the contribution of IgG to host defense. We are unaware of any published reports describing the IgG subclass response of LJP subjects to protein and polysaccharide antigens on the surface of A. actinomycetemcomitans. The primary objectives of this proposal are to: 1. Determine the IgG subclass response of LJP subjects to isolated surface antigens of A. actinomycetemcomitans, including outer membrane proteins and lipopolysaccharide. 2. Define the subclass of opsonic IgG antibody known to be present in sera of some LJP subjects. 3. Identify the outer membrane constituent recognized by opsonic IgG antibody against A. actinomycetemcomitans. The information derived from the proposed studies will provide important insight into the nature and biological consequences of the IgG antibody response of localized juvenile periodontitis subjects to A. actinomycetemcomitans.