Pretreatment with T Cell Receptor Peptides Using a Conventional Immunization Protocol Does Not Induce Effective Protection against Autoimmune Encephalomyelitis

Abstract

It was previously reported that vaccination with synthetic peptides corresponding to the CDR2 or CDR3 region of T cell receptor (TCR) protected susceptible animals from the development of experimental autoimmune encephalomyelitis (EAE). However, recent studies by several research groups have revealed that TCR peptide therapy often confers little or no protection from autoimmune diseases. In the present study, we attempted to find more appropriate peptides that is capable of conferring effective protection against the development of EAE. Four peptides corresponding to parts of the Vβ region (13–23, 24–36, 39–59, and 64–74) were selected by epitope scanning and hydrophilicity searching, and their protective abilities were tested. All these peptides were, however, ineffective in protecting rats from the disease. We also generated three different synthetic peptides corresponding to the TCR J region of encephalitogenic T cells. Vaccination with the J-region peptides did not protect animals from the development of EAE. Rather, one of the peptides (Vβ-DSS-Jβ2.6) enhanced the clinical severity of EAE and induced fatal disease in some rats. Taken together, TCR peptide therapy appears to be generally ineffective and elucidation of the mechanism by which EAE is enhanced after TCR peptide vaccination should provide insight into the pathogenesis of this disease.