T-Bodies: Chimeric T-Cell Receptors with Antibody-Type Specificity

Abstract

The variable regions of the T-cell receptor for antigen (TCR) and antibodies serve as recognition elements, enabling T and B cells to bind antigen with high specificity. Nevertheless, the complex recognition requirements of T cells, which respond to antigen only in the context of a self MHC molecule, do not permit the generation of antigen-specific lymphocytes, which could serve as universal effector cells. To enable the generation of non-MHC-restricted T cells of predetermined specificity, we took advantage of the similarity between the antibody and the T-cell molecule and expressed in T-cell lines chimeric T-cell receptor (cTCR) genes in which the TCR variable region is replaced by an antibody variable region of defined specificity. In another design, the antibody recognition unit has been used in the form of a single-chain Fv (scFv) to create hybrid molecules with other receptor subunits, including the ζ chain of the CD3 complex and the γ chain of the high-affinity receptor for IgE (FcϵRI). T-cell lines transfected with the chimeric TCR or scFvR exhibit cytotoxicity or secrete cytokines in response to antigen displayed either on a solid substrate or on the surface of target cells. We describe here the various configurations of the chimeric receptors that we have produced. Technical aspects, including the choice of vector, antibody sequences, and triggering molecule, are reviewed.[ep [rs