Previous work completed at the Clinical Research Center for Periodontal Diseases has indicated that antibody reactive with Actinobacillus actinomycetemcomitans (Aa) may be protective. Aa seropositive early onset periodontitis (EOP) patients have decreased disease severity compared to patients lacking antibody. The specific antigen-antibody interactions and the immune mechanisms involved in providing this protection have not been determined. We hypothesize that antibody responses to certain specific antigens are important in the protective antibody response. We further hypothesize that these specific antigens include the leukotoxin produced by Aa, and/or cell surface antigens. To test this hypothesis we propose to examine the antibody response to the Aa leukotoxin in EOP patients using western blots with limiting dilution analysis. This will allow us to assess the antibody response in terms of presence/absence of specific antibody, antibody titer, antibody class and subclass distribution, and antibody avidity. The responses will then be compared to the clinical status of the subjects in terms of disease severity and extent in order to determine which antibody-antigen interactions are important in the protective antibody response. This requires a large number of EOP patients for study. We have already collected sera and clinical data from 284 EOP subjects. By identifying and characterizing the specific antibody interactions responsible for the protective antibody response in EOP patients, a better assessment of a patient's clinical status and prognosis may be possible. Further, this analysis may provide insight into the pathogenesis of periodontal destruction. The antigens involved in these interactions may also make good candidates for an Aa vaccine.