International Immunology, Vol. 15, No. 11, pp. 1379-1387,
November 2003
© 2003 Japanese Society for Immunology
Chimeric ß2 microglobulin/CD3
polypeptides expressed in T cells convert MHC class I peptide ligands into T cell activation receptors: a potential tool for specific targeting of pathogenic CD8+ T cells
1 MIGAL, Galilee Technology Center, South Industrial Zone, Kiryat Shmona, 11016, Israel 2 Department of Biotechnology, Tel Hai Academic College, Upper Galilee, 12210, Israel 3 Department of Pharmacology, The Royal Danish School of Pharmacy, Jagtvejen 160,DK 2100 Copenhagen, Denmark
Correspondence to: G. Gross, MIGAL, Galilee Technology Center, South Industrial Zone, PO Box 831 Kiryat Shmona 11016, Israel. E-mail: gidi{at}migal.org.il
Transmitting editor: I. Pecht
CD8+ T cells are key mediators of transplant rejection and graft-versus-host disease and contribute to the pathogenesis of autoimmune diseases. We tested whether TCR ligands can be converted into T cell activation receptors, redirecting genetically modified T cells at pathogenic CD8+ T cells. For this purpose we exploited the ability of the non-polymorphic ß2 microglobulin light chain to pair with all MHC class I heavy chains. In this report we describe the design and expression in a T cell hybridoma of two modalities of ß2 microglobulin polypeptides, fused with the transmembrane and intracellular portion of CD3
chain. In the absence of a particular antigenic peptide, the chimeric product associates with different endogenous MHC class I heavy chains and triggers T cell activation upon heavy chain cross-linking. When an antigenic peptide is covalently attached to the N-terminus of the chimeric polypeptide, transfectants express high level of surface peptide–class I complexes and respond to antibodies and target T cells in a peptide-specific manner. Our results provide the basis for a universal genetic approach aimed at antigen-specific immunotargeting of pathogenic CD8+ T cells.
Keywords: adoptive immunotherapy, chimeric MHC protein, cytotoxic T lymphocyte, T cellre-programming, T cell specificity
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