SELECTIVE ELIMINATION OF ANTIGEN-SPECIFIC LINE T-CELLS AND EX-VIVO ANTIGEN-PRIMED LYMPH-NODE CELLS BY ANTIGEN-TARGETED DRUG-LABELED ANTIGEN-PRESENTING CELL-MEMBRANES

Since antigen-specific autoaggressive T cells have been found in assoc iation with many autoimmune diseases, a treatment to eliminate such an tigen-specific T cell clones was developed. The complex of peptide ant igen and class II MHC protein is used to target a cytotoxic drug to an tigen-specific T cells, The drug is bound covalently to antigen-presen ting cells (APC) and protein antigens (Ag) are added to the cells for processing and presentation of peptides, The APC contain class II MHC (Ia) protein to present the peptide Ag to the T cell receptor and adhe sion proteins for optimal interaction with the T cell, Either the Ag-b earing intact APC or Ia(+) membranes shed or released spontaneously fr om them were used as drug carriers to target the drug to the T cells, The drugs being used are phototoxic compounds, When irradiated with li ght of an appropriate wavelength, they give off toxic free radicals an d singlet oxygen, These toxic by-products are short-lived and damage c ells only in their immediate vicinity, cutting down on nonspecific sid e effects, APC from thymus cells, or their shed membranes bearing Ia-A g peptide complexes, were able to target the phototoxic drug specifica lly to Ag-specific T line cells and ex vivo Ag-specific lymph node cel ls, Proliferation of the target T cells was inhibited at a three to fo ur times lower drug concentration than required to affect control T ce lls. The Ag-specific effect was inhibited by anti-Ia antibody and by d rug-free membranes carrying the Ag-Ia complex. This indicated that the antigen-specific phototoxic effect was mediated by interaction of the Ag-Ia complex with the T cell receptor. (C) 1997 Academic Press.