GENETICS OF ANTIBODIES TO PERIODONTAL PATHOGENS

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Caries and periodontal diseases afflict most individuals at some time during life and are the major causes of tooth loss in all age groups. The factors which determine resistance or susceptibility to these diseases are unknown. These diseases are caused by dental plaque associated microorganisms, which colonize the tooth surface and gingival sulcus. The ability of these organisms to colonize the oral cavity depends upon their adherence to the tooth surface or other bacteria. Specialized cell surface structures mediate the adherence of bacteria to oral surfaces, and antibodies directed against these structures have been shown to inhibit bacterial adherence and colonization. An attractive explanation for differences in disease susceptibility is genetically controlled variations in the antibody response to adherence associated structures on periodontal pathogens. The proposed project, which is based on previous studies of genetic control of serum and salivary antibody responses to SRBC, is a detailed study of genetic control of serum and salivary antibody responses to a purified protein antigen (T-1) which mediates the adhrerence of Actinomyces viscosus strain T14V to saliva coated hydroxyapetite surfaces. Experiments will be done in inbred mice and a radioimmunoassay will be used to measure Ig isotype specific and responses to T-1 and A. viscosus strain T14V. A strain survey will be done and appropriate parental strains will be selected for genetic analysis. The serum and salivary anti-T-1 antibody responses of the parental strains, F1 hybrid and backcross mice will be analyzed, as well as the responses of congenic and recombinant inbred mice. Segregation and linkage analysis of these data will substantiate the hypothesis that serum and salivary antibody responses to T-1 are genetically determined and provide insight into the nature of this control. Different, well characterized anti-T-1 sera and salivas will be tested in an in vivo adsorption inhibition assay to correlate magnitude and isotype of the anti-T1 response with the ability to inhibit the adhrence of A. viscosus strain T14V cells to an "in intro tooth surface." These studies will hopefully provide an understanding of the role of genetics in determining disease susceptibility and determine the characteristics of protective anti-T-1 antibody responses. This information would be useful in the development of immunization protocols in humans to prevent or control periodontal diseases.