IN-VIVO SURVIVAL OF VIRAL ANTIGEN-SPECIFIC T-CELLS THAT INDUCE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

A peptide derived from the human papillomavirus L2 protein is recogniz ed by a myelin basic protein (MBP)-specific T cell clone from a multip le sclerosis patient and by MBP-specific autoantibodies purified from multiple sclerosis brain tissue. We now show in mice that low doses of this papillomavirus peptide were optimal in selecting a subpopulation of papillomavirus peptide-specific T cells that cross-reacted with MB P(87-99) and with an unrelated viral peptide derived from the BSLF1 pr otein of Epstein-Ban virus (EBV). These low dose viral peptide-specifi c T cell lines were highly encephalitogenic. Splenocytes from mice tra nsferred with viral peptide-specific T cells showed a vigorous respons e to both the papillomavirus and MBP peptides, indicating that viral a ntigen-specific T cells survived for a prolonged time in vivo. The EBV peptide, unable to prime and select an autoreactive T cell population , could still activate the low dose papillomavirus peptide-specific ce lls and induce central nervous system (CNS) autoimmunity. Cytokine pro files of papillomavirus peptide-specific encephalitogenic T cells and histopathology of CNS lesions resembled those induced by MBP. These re sults demonstrate conserved aspects in the recognition of the self-ant igen and a cross-reactive viral peptide by human and murine MBP-specif ic T cell receptors. We demonstrate that a viral antigen, depending on its nature, dose, and number of exposures, may select autoantigen-spe cific T cells that survive in vivo and can trigger autoimmune disease after adoptive transfer.