(SLJ/J x PL/J)F1 mice immunized with myelin basic protein (MBP) were shown to develop T cell reactivity to an additional myelin autoantigen, proteolipid protein (PLP), during the course of relapsing experimental allergic encephalomyelitis. T. cell reactivity to PLP, as measured by delayed type hypersensitivity in vivo or proliferation in vitro, develops early during the course of disease by is consistently weaker than the response to MBP. Sensitization of the host to this second myelin encephalitogen is due to I-A restricted T cell recognition of endogenous PLP and not due to contamination of our purified MBP with PLP, as determined by rigorous examination of protein stocks used in these experiments. The induction of host tolerance to PLP prior to immunization with MBP had no detectable effect on the incidence or severity of disease expression, suggesting that MBP is the primary T cell target during all stages of relapsing disease in this animal model. Nevertheless, this system may provide a relevant model for development of myelin autoreactivity in multiple sclerosis, where T cell reactivity to MBP, PLP or to both autoantigens has been recently reported. Results have been published in the Journal of Neuroimmunology.