REGULATION OF ANTIBODY RESPONSE TO BACTERIAL ANTIGENS

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The long term objective of this project is to establish the precise mechanisms by which T-cells regulate the antibody response to bacterial polysaccharide antigens (BPA) and how this information can be used in the prevention of specific diseases (dental caries, peridontal disease, pneumonia, etc.). It is known that aberrent immune responses to BPA play a role in the predisposition to some of these diseases, such as juvenile peridontitis. Three major goals will be accomplished in the proposed studies. First, monoclonal antibodies to T-cell surface and products of the I region of the H-2 complex will be used to better define the complex regulatory role that T-cells play in antibody production. Four monoclonal antibodies (anti-Ia, anti-I-J, and anti-Lym 22 and 21) and an allo-antiserum (anti-Qa 1) will be used to further characterize suppressor (Lyt 2+) and amplifier (Lyt 1+) T-cells which regulate the antibody response to pneumococcal polysaccharide type III (SSS-III). The characterization of the regulatory cells will be done by the depletion of specific subpopulations with antibody and complement and then testing the residual cells for activity. Second, an in vitro system for the induction of antibody response to SSS-III will be established in order to identify the cells involved in the production of factors released from regulatory T-cells. This analysis will be accomplished, first, by using whole spleen cells, then enriched populations and finally T-cell clones. By this in vitro system we will also determine the recognition signals involved in the activation of regulatory T-cells. We have preliminary evidence that regulatory T-cells in this system (SSS-III) recognize idiotypic determinants (ID) on B cells. It is possible that such a recognition of ID in BPA systems replaces the need to recognize self MHC determinants which is known to occur in most non-bacterial antigens. Third, we will determine if the same immunoregulatory mechanisms established for SSS-III can be directly applied to other streptococci, e.g., Streptococcus mutans, the etiologic agent for dental caries, and three other BPA (meningococcal A, C and Haemophilus influenzae) known to be immunogenic in mice.