T Cell Hybridomas And Related Compositions And Methods For Assaying And Modulating T Cell Receptor-Mediated Immune Responses

摘要

The present invention provides T cell hybridomas and related compositions and assay systems for investigative, diagnostic, and therapeutic use in modulating T cell receptor (TCR)-mediated immune response. The T cell hybridomas of the invention are typically constructed by fusing a naïve or early central memory T cell isolated from a mammalian subject with an immortalizing fusion partner (e.g. mammalian lymphoid tumor cell) to yield clonal T cell hybrids. The resulting T cell hybridomas exhibit antigen (Ag)-specific proliferation responsiveness over a background level of proliferation of the hybridomas. These hybridomas are useful for screening, identifying, and characterizing T cell immune modulatory agents, for example recombinant T cell receptor ligands (RTLs) and other agents that can modulate TCR-mediated T cell immune responses. Ag-specific proliferative response profiles exhibited by the T cell hybridomas of the invention show sufficient amplitude, sensitivity and fidelity to distinguish and/or quantify the presence and/or activity of a test RTL or other test modulatory agent in screening and sensitivity assays employing the hybridomas. These and other aspects of the invention yield powerful tools and methods for developing and characterizing novel RTLs and other immune modulatory agents for use in treating immune disorders, including a wide range of autoimmune diseases, in mammals.