Redirecting the complete T cell receptor/CD3 signaling machinery towards native antigen via modified T cell receptor.
We show that a chimeric T cell receptor (TCR) beta chain consisting of a single-chain Fv portion derived from a monoclonal antibody and the full TCR beta chain is able to assemble functionally with endogenous TCR/CD3 components and transfer the antibody specificity as well as the TCR specificity into TCR beta- as well as into TCR beta+ T cells. This allows the incorporation new non-major histocompatibility complex-restricted ligand specificities into the intact TCR/CD3 complex which can exploit the full range of biological activities of the endogenous TCR signaling machinery. This approach can provide wider opportunities to redirect T cells to virus or tumor antigen-bearing cells.
Brocker
T
T
Basel Institute for Immunology, Switzerland.
Riedinger
M
M
Karjalainen
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006389:Hemagglutinins, Viral / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000494:pharmacology; D006801:Humans; D006825:Hybridomas; D007128:Immunoglobulin Fragments / Q000737:chemistry; D009980:Influenza A virus / Q000737:chemistry / Q000276:immunology; D015458:Leukemia, T-Cell; D051379:Mice; D008806:Mice, Inbred AKR; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection / Q000276:immunology; D014407:Tumor Cells, Cultured
D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007128:Immunoglobulin Fragments; D010455:Peptides; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; C055966:immunoglobulin Fv