Protection from experimental allergic encephalomyelitis conferred by a monoclonal antibody directed against a shared idiotype on rat T cell receptors specific for myelin basic protein

摘要

Immunizing Lewis rats with guinea pig myelin basic protein (MBP) yielded an encephalitogen specific, Ia-restricted, rat-mouse T cell hybridoma 5.10, which was used to establish a clonotypic mAb (10.18) that binds to and precipitates the rat TCR. By two-dimensional gel electrophoresis, the rat TCR was shown to consist of two disulfide- linked peptide chains with mol wt of 48,000 and 39,000. 10.18 binds the majority of cells in MBP-specific T cell lines that are capable of transferring experimental allergic encephalomyelitis (EAE) to Lewis rat recipients, but does not bind to either a purified protein derivative of tuberculin-specific cell line or an OVA-specific line. Furthermore, soluble 10.18 can block antigen-specific stimulation of hybridoma 5.10 but cannot control hybridomas, while immobilized 10.18 stimulates 5.10, but cannot control the hybrids. Though 10.18+ cells are very rare in normal rats, increase of 10.18+ cells is observed in MBP-primed paralyzed rats. Finally, when 10.18 is injected into MBP-primed Lewis rats, EAE is abrogated. We have thus characterized EAE as a "mono- idiotypic" autoimmune disease.