WO1996013593A3 - Soluble single chain t cell receptors - Google Patents

Abstract

A fusion protein, comprising a carrier protein connected by a peptide tether to a single chain T cell receptor molecule, consisting of a Vα segment linked to a Vβ segment of the T cell receptor, is disclosed. Also disclosed is a soluble single chain T cell receptor molecule with a conformation that is essentially functionally indistinguishable, based upon reactivity to clonotype-specific antibodies, from that appearing on the surface of T cells. The invention also concerns nucleic acid fragments encoding the fusion protein, expression vectors comprising a nucleic acid fragment encoding the fusion protein, host cells containing such expression vectors, and antibodies to the single chain T cell receptor or to the fusion protein. The invention further pertains to methods of isolating and purifying the fusion proteins, as well as isolating and purifying soluble, single chain T cell receptors. In addition the invention pertains to various uses of soluble TCR fusion protein and isolated single chain TCR. The proteins can be used in molecular assays designed to measure their binding to ligands, including MHC/HLA-peptide antigen complexes or TCR-specific antibodies. Such assays are useful for the detection of agents that block the TCR-ligand interaction. The soluble TCR proteins can also be used to immunize animals, including humans, to produce TCR-specific antibodies. In addition, either in their native or denatured conformation the proteins can be used to vaccinate animals, including humans, in order to suppress the immune response of T cells bearing TCR that share antigenic epitopes with the vaccinating protein.