This study takes advantage of the predominant usage of Vbeta8.2 by the TCRs of encephalitogenic T cells specific for myelin basic protein. Vaccinia virus recombinants expressing Vbeta8.2 (VVbeta8.2) 8.2) and Vbeta3 (VVbeta 3) proteins were constructed, and their abilities to confer protection against experimental autoimmune encephalomyelitis (EAE) induction in H-2u mice were examined. Mice immunized with VVbeta8.2 developed very mild EAE by comparison with mice that were vaccinated with VVbeta3, which developed severe clinical symptoms. This reduction in EAE correlated with a diminished T cell proliferative response to myelin basic protein in the mice that received VVbeta8.2 compared with that in mice receiving VVbeta3.