Persistent expression of experimental autoimmune encephalomyelitis (EAE)-specific Vβ8.2 TCR spectratype in the central nervous system of rats with chronic relapsing EAE

Monitoring the TCR repertoire is indispensable for the assessment of T cell-associated autoimmune diseases and subsequent TCR-based immunotherapy, In the present study, we examined the TCR repertoire of spinal cord T cells of Lewis rats by CDR3 spectratyping during chronic relapsing experimental autoimmune encephalomyelitis (EAE) induced by immunization with spinal cord homogenate, It was found that V beta 8.2 spectratype with the shortest CDR3 expanded oligoclonally throughout the course of the disease. In addition, V beta 12 spectratype expansion was observed at the first and second attacks of EAE, Sequence analysis revealed that clones with the DSSYEQYF sequence, which is a representative sequence of myelin basic protein (MBP)-reactive T cell clones, constituted the predominant population in the V beta 8.2 family. Surprisingly, V beta 12 also used the identical amino acid sequence in the CDR3 region, These findings indicate that although infiltrating T cells in the central nervous system are activated polyclonally, the TCR repertoire remains unchanged throughout the course. Moreover, the finding that the predominant CDR3 amino acid sequence of V beta 8.2 and V beta 12 spectratypes is identical with that of MBP-induced EAE suggests that a single Ag in spinal cord homogenate, possibly MBP, is involved in disease development.