ANTI-IDIOTYPE REGULATION OF TIMOTHY IGE FORMATION

本课题的目的是研究体外诱导

The objective of this proposal is to study the in vitro induction of antigen-specific suppressor T cells by anti-idiotypic antibodies and soluble antigen-specific suppressor factors. Preliminary studies indicate that anti-idiotypic antibody (anti-Id) and affinity-purified timothy grass pollen AgB-specific suppressor factor (TSF) and anti-idiotype factor (anti-Id factor) induce significant levels of suppressor T (TS) cells in vitro. The proposed experiments will attempt to 1) derive the optimal culture conditions for the induction of TS cells, 2) determine the nature of the TS cells induced (TS1 and TS2), 3) determine the role of Fc+ cells in "presentation" of anti-Id, TSF, and anti-Idfactor to T cells, and 4) determine the cell surface antigen characteristics of the cell induced by anti-Id-bound Fc+ cells. Important new information regarding the constant region of TSF and anti-Id factor would be obtained from studies indicating that Fc+ cells play a role in the induction of TS cells by these factors secreted from TS1 and TS2 cells. The amounts of IgG or IgE antibody formed and the levels of TSF and anti-Id factor extracted from enriched TS1 and TS2 cell populations will be determined by ELISA methods. The availabiltiy of monoclonal anti-T-helper factor (anti-THF) antibody will permit us to determine if the idiotypic determinants expressed on T-helper, T-suppressor, and B cells are identical or only appear identical due to the heterogeneity of our rabbit anti-THF and anti-IgEid (anti-Id) antibodies. One of our long-term goals is to develop materials that will suppress IgE responses of timothy-sensitive patients. We have proposed trying to develop antigen-specific human TS cells by using 1) affinity-purified human timothy IgE to prepare anti-idiotypic antibodies, 2) photooxidized timothy AgB in cultures with macrophage-depleted peripheral blood lymphocytes, and 3) anti-idiotypic antibody made against murine T and B cell products that react to the identical antigenic determinant as humans allergic to timothy pollen. These studies will involve the in vitro cultures of peripheral blood lymphocytes in mini-Marbrook chambers. The harvested cells will be analyzed for their ability to suppress timothy-specific IgE formation in vitro.