The reactivity of the immune system against an antigen may be profoundly and specifically changed--enhanced or suppressed--by an administration of antibodies which are specific for the unique idiotopic determinants (Id) of the antigen receptor. The long-term objective of our research is to understand the molecular and cellular mechanisms of immune regulation by anti-idiotopic antibodies (anti-Id) so that this potentially powerful tool can be used with predictable results. The experimental animal model to be used is the antibody response of mice to a pneumococcal antigen phosphorylcholine (PC). The PC-specific immunoglobulin receptors on majority of b cells (as well as on t cells, perhaps) bear the T15 idiotype, which is a complex of greater than or equal to seven distinct Id determinants detected by monoclonal anti-Id. Some of these anti-Id recognize determinants within the paratope and compete with the antigen for binding (i.e., """"""""internal images"""""""" of PC) while other anti-Id bind to determinants distant from the paratope. The mechanisms involved in activation and suppression of B and T cells by different receptor site-specific anti-Id will be studied in vitro and in vivo. The ability of anti-Id to activate B cell proliferation and antibody synthesis will be studied in respect to the form of anti-Id presentation, the requirement of Fc fragment, synergistic action among different anti-Id or between anti-Id and antigen, and the role of T cells and their products. The mechanisms of B cell suppression will be explored along similar lines. The in vivo studies will compare the ability of different anti-Id to induce anti-PC antibody and protection against pneumococcal infection. Using an anti-Id that recognizes a PC-specific determinant expressed exclusively on IgA, we will attempt to induce a specific IgA response to pneumococcus. The requirement of T cells and their role in the stimulation of antibody by anti-Id will be studied in inbred and congenic mice with distinct idiotopic profiles determined previously in our laboratory. Finally, the cellular mechanisms of immune suppression by anti-Id in vivo also will be studied.
