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 ongoing studies of genetic control of the serum antibody responses to Actinomyces viscosus, is a detailed study of genetic control of the specificity of serum antibodies to purified type 1 fimbriae (T-1) which mediate the adherence of Actinomyces viscosus strain T14V to saliva coated hydroxyapetite surfaces. Experiments will be done in inbred mice and isoelectric focusing and idiotype specific ELISA's will be used to determine the spectrotypes and idiotypes of anti-T1 antibodies. A strain survey will be done and appropriate parental strains will be selected for genetic analysis. The serum 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 analyses of these data will substantiate the hypotheses that the specificity of serum antibodies to T-1 are genetically determined and provide insight into the nature of this control. Different, well characterized anti-T-1 sera will be tested in an in vitro adsorption inhibition assay to correlate the spectrotype and idiotype of anti- T1 antibodies with their ability to inhibit the adherence of A. viscosus strain T14V cells to an "in vitro tooth surface." These studies will hopefully provide an understanding of the role of genetics in determining disease susceptibility and determine the characterisitcs 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.