SOLUBLE HETERODIMERIC T CELL RECEPTORS AND THEIR ANTIBODIES

摘要

Heterodimeric T cell receptor proteins, comprising alpha and beta subunits joined by at least one disulfide bond, are disclosed. The alpha and beta subunits are generated as chimeric polypeptides, utilizing zeta chains or constant regions of IgG1 as chimeric partners. Also disclosed are soluble heterodimeric T cell recpetor molecules with a conformation essentially indistinguishable from that appearing on the surface of T cells. The invention also concerns DNA encoding the heterodimeric TCR, transfer vectors comprising DNA encoding the heterodimeric TCR, and host cells containing such transfer vectors. In addition, the invention pertains to various uses of heterodimeric 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 heterodimeric TCR 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.