Characterization of the Antigen Specificity and TCR Repertoire, and TCR-Based DNA Vaccine Therapy in Myelin Basic Protein-Induced Autoimmune Encephalomyelitis in DA Rats

Abstract

Like Lewis rats, DA rats are an experimental autoimmune encephalomyelitis (EAE)-susceptible strain and develop severe EAE upon immunization with myelin basic protein (MBP). However, there are several differences between the two strains. In the present study we induced acute EAE in DA rats by immunization with MBP and MBP peptides and examined the Ag specificity and TCR repertoire of encephalitogenic T cells. It was found that although immunization with MBP and a peptide corresponding to its 62–75 sequence (MBP62–75) induced clinical EAE, the responses of lymph node T cells isolated from MBP-immunized rats to MBP62–75 was marginal, indicating that this peptide contains major encephalitogenic, but not immunodominant, epitopes. The TCR analysis by CDR3 spectratyping of spinal cord T cells revealed that Vβ10 and Vβ15 spectratype expansion was always found in MBP62–75-immunized symptomatic rats. On the basis of these findings, we examined the encephalitogenicity of Vβ10- and Vβ15-positive T cells. First, the adoptive transfer experiments revealed that Vβ10-positive T line cells derived from MBP62–75-immunized rats induced clinical EAE in recipients. Second, administration of DNA vaccines encoding Vβ10 and Vβ15, alone or in combination, ameliorated MBP62–75-induced EAE. Collectively, it was strongly suggested that Vβ10- and Vβ15-positive T cells are encephalitogenic. Analyses of the Ag specificity and T cell repertoire of pathogenic T cells performed in this study provide useful information for designing specific immunotherapies against autoimmune diseases.

Therapeutic effect of mbp immunodominant peptides encapsulated in nanovehicles in the development of experimental autoimmune encephalomyelitis in DA rats

“…Studies of EAE induction in DA rats with peptides of guinea pig myelin had shown that only GPBP (62-84) could induce EAE significantly and GPBP (68-88), to a lesser extent [17]. We detected no notable activity of autoantibodies against these peptides, which was in agreement with earlier data pointing to the encephali togenic rather than the immunodominant role of MBP (62-75) [18].…”

Characterization of the T cell receptor repertoire in the Japanese neuromyelitis optica: T cell activity is up-regulated compared to multiple sclerosis

“…If the TCR usage by pathogenic T cells is known, TCR-based immunotherapy could be achieved in human demyelinating diseases. As reported previously [23,24], encephalitogenic T cells induced in DA rats by immunization with a peptide corresponding to the 62-75 sequence of MBP (MBP 62-75 ) mainly used Vβ10 and Vβ15 and administration of DNA vaccines encoding Vβ10 and Vβ15 successfully ameliorated MBP 62-75 -induced EAE.…”

B- and T-Cell Responses in Group A Streptococcus M-Protein- or Peptide-Induced Experimental Carditis

“…In our study, only one B-repeat region peptide (M5-B.1, aa 111 to 130) produced a strong T-cell response in rM5-immunized rats. However, it is often found that T cells taken from animals that have been immunized with whole protein show minimal proliferative responses when stimulated with individual peptides from the whole protein (28). This can be attributed to the low frequencies of T cells in the periphery that respond to each individual peptide.…”