Successful TCR-based immunotherapy for autoimmune myocarditis with DNA vaccines after rapid identification of pathogenic TCR

The identification of TCRs of autoimmune disease-inducing T cells within a short period of time is a key factor for designing TCR-based immunotherapy during the course of the disease. In this study, we show that experimental autoimmune carditis-associated TCRs, V beta 8.2 and V beta 10, were determi ned by complementarity-determining region 3 (CDR3)-spectratyping analysis a nd subsequent sequencing of the CDR3 region of spectratype-derived TCR clon es. Immunotherapy targeting both VP beta 8.2 and V beta 10 TCRs using mAbs and DNA vaccines significantly reduced the histological severity of experim ental autoimmune carditis and completely suppressed the inflammation in som e animals. Since depletion or suppression of one of two types of effector c ells does not improve the severity of the disease significantly, combined T CR-based immunotherapy should be considered as a primary therapy for T cell -mediated autoimmune diseases. TCR-based immunotherapy after rapid identifi cation of autoimmune disease-associated TCRs by CDR3 spectratyping can be a pplicable, not only to animal, but also to human autoimmune diseases whose pathomechanism is poorly understood.