Use of antibodies as carriers for T-cell epitopes.

Abstract

T cells recognize proteolytic fragments of proteins (= immunogenic peptides or T-cell epitopes) presented on HLA molecules. Presentation of peptides of exogenous proteins normally occurs on HLA class II structures, while epitopes of endogenous or viral proteins are presented on HLA class I molecules. The type of antigen presenting cell is also of importance for the immune response evolving, since presentation by dendritic cells is capable to trigger a proliferative and cytotoxic immune response [1], while presentation by macrophages favors a proliferative response. In the context of allergic reactions, it is specifically interesting that peptide presentation on aberrantly HLA-DR expressing cells (i.e. thyrocytes in Hashimoto thyroiditis or keratinocytes after interferon treatment) is able to induce clonal anergy, which would be an interesting approach to stop allergic reactions. An insufficient interaction with accessory cell molecules is probably responsible for this failure of a proliferative response [2]. To further evaluate the importance of the type of the antigen presenting cell, we established a system which allows to select the antigen presenting cell. Tetanus toxoid (TT) or an HLA class II binding peptide of TT (residue 830–843, P2) was covalently coupled to anti-CD4, anti-CD8 or anti-CD2 monoclonal antibodies. T cells themselves were chosen as potential antigen presenting cells, as they express HLA-DR after activation and are able to process and present antigens [3], but are unable to capture the antigen. T-cell lines or clones were incubated with these constructs, the proliferative response of TT or P2-spe-cific T-cell clones was evaluated.