We examined the TCR repertoire used by naive SJL mice in their in vitro spontaneous response to proteolipid protein (PLP) 139-151 by VÎ²-JÎ² spectratyping and compared it to that used after immunization with the peptide. T cells from immunized mice use the public rearrangement VÎ² 10-JÎ² 1.1, but naive mice do not; in contrast, TCR CDR3-Î² rearrangements of VÎ² 18-JÎ² 1.2 and VÎ² 9-JÎ² l.2 consistently are associated with the spontaneous response. T cells involved in spontaneous and induced responses can each recognize PLPI39-I51presented in vivo, but its s.c. administration has different consequences for the two repertoires. Four days after immunization, T cells associated with spontaneous responsiveness appear in the draining lymph nodes but disappear by day 10 and never appear elsewhere. Simultaneously, VÎ² 10-JÎ² 1.1 T cells are likewise activated in the lymph nodes by day 4 and spread to the spleen by day 10. Eight- to 10-wk-old naive mice use a narrower repertoire of TCRs than do immunized age-matched mice. Induced VÎ² 10-JÎ² 1.1 T cells home to the CNS during experimental autoimmune encephalomyelitis, whereas we failed to detect VÎ² 18-JÎ² 1.2 and VÎ² 19-JÎ² 1.2 TCR rearrangements in the CNS. Thus, we observe that administration of PLP139-151primes a T cell repertoire distinct from the one responsible for spontaneous responsiveness. This "immunized" repertoire substitutes for the naive one and becomes dominant at the time of disease onset. Copyright Â© 2008 by The American Association of Immunologists, Inc.