Characterization of T cell receptor associated with the development of P2 peptide-induced autoimmune neuritis

To characterize experimental autoimmune neuritis (EAN)-inducing T cells in more detail, we performed CDR3 spectratyping analysis and found oligoclonal expansion of several V beta spectratypes in nerve-infiltrating T cells. V beta 5 expansion was observed all the stages examined, whereas V beta 8.2 and V beta 17 expansion was mainly found at the peak and preclinical stages, respectively. Since V beta 5 expansion persists throughout the course of the disease, V beta 5(+) T cells are judged to be the main effector cells. V beta 8.2(+) and V beta 17(+) T cells may also be pathogenic but are not the main effecters because expansion of these spectratypes was found at a limited period of time. Sequence analysis revealed that V beta 5, V beta 8.2 and V beta 17 spectratype-derived TCR clones possess their own dominant sequences in the CDR3 region with no homology among the clones. These findings suggest that polyclonally activated T cells are involved in the formation of the nerve lesion. Furthermore, vaccination with V beta 5 DNA, but not with V beta 10 DNA, suppressed the development of EAN significantly. Collectively, these findings indicate that determination of autoimmune disease-associated TCR by CDR3 spectratyping provides useful information for designing TCR-based immunotherapy for the disease. (C) 2000 Elsevier Science B.V. All rights reserved.