Prevention and reversal of experimental autoimmune myasthenia gravis by a monoclonal antibody against acetylcholine receptor-specific T cells

We have recently described an algorithm to design, among others, peptides w ith complementarity contour to autoimmune epitopes, Immunization with one s uch peptide resulted in a monoclonal antibody (mAb), termed CTCR8, that spe cifically recognized V beta 15 containing TCR on acetylcholine receptor (AC hR) alpha -chain residue 100-116-specific T cells. CTCR8 was found to label the cell surface of AChR100-116-specific T cell lines and clones, immunopr ecipitate the TCR from such cells, and block their proliferative responses to AChR alpha 100-116, In the present report, we have found that there is a marked reduction in IFN-gamma and no effect on IL-10 production in a CTCR8 -treated AChR alpha 100-116-specific T cell line. Interestingly, when AChR1 00-116-primed, primary T cells were stimulated with peptide and treated wit h CTCR8, there was once again inhibition of IFN-gamma but also marked stimu lation of IL-10 production. The change in the Th1/Th2 cytokine pro file was paralleled by a reduction in AChR-specific IgG2a and IgM with no effect on IgG1, Remarkably, the most profoundly inhibited Ab population was that whi ch causes experimental autoimmune myasthenia gravis (EAMG) by reaction with the main immunogenic region (alpha 61-76) of the AChR Based on these resul ts, CTCR8 was tested for prophylactic and therapeutic effects in EAMG, EAMG induced by immunization with purified native Torpedo AChR was both inhibit ed and reversed by CTCR8, These findings suggest a means to produce therape utic mAb for the treatment of autoimmune diseases, (C) 2001 Academic Press.