Multiple sclerosis (MS) is a chronic autoimmune neurological disease characterized by infiltration of peripheral inflammatory cells to the central nervous system (CNS) and demyelination of CNS white matter. Epidemiological evidence suggests a possible infectious trigger. One potential mechanism by which an infectious agent may trigger MS is via molecular mimicry wherein T cells generated against foreign epitopes cross-react with self-myelin epitopes, such as myelin basic protein (MBP), with sufficient sequence similarity. It has been previously reported that an MBP(85-99)-reactive T cell clone derived from an MS patient cross-reacted with multiple bacterial-derived mimic peptides in vitro. We show that the same mimic peptides can induce clinical disease in two different strains of mice transgenic for both a human MBP(85-99)-specific TCR and HLA-DR2 (MHC II), albeit with different disease patterns - relapsing-remitting vs. monophasic. Interestingly, clinical disease correlates with CNS infiltration of CD4(+) T cells and F4/80(+) macrophages, but not with in vitro proliferative or cytokine responses of splenocytes in response to either MBP(85-99) or its mimics.