Fulminant spontaneous autoimmunity of the central nervous system in mice transgenic for the myelin proteolipid protein-specific T cell receptor

Proteolipid protein (PLP)-139-151 is the dominant encephalitogenic peptide that induces experimental autoimmune encephalomyelitis (EAE) in SJL (H-2(s) ) mice. To examine the contribution of T cell receptor (TCR) specificity in the induction of EAE, we generated transgenic mice expressing the rearrang ed TCR genes from an encephalitogenic or a nonencephalitogenic PLP-139-151/ I-A(s)-specific T cell clone. Both types of transgenic lines developed spon taneous EAE, but, remarkably, the lines expressing the TCR from the nonence phalitogenic clone showed increasingly higher frequencies of disease (60-83 %) in progressive SJL backcrosses and could not be propagated an the suscep tible background. The T cells from the transgenic: mice were not tolerized, because they responded vigorously to the antigen in vitro and mediated EAE when the mice were immunized with antigen. Besides being the only descript ion of a TCR transgenic mice for the PLP-139-151/I-A(s) epitope, the result s demonstrate that the TCR from a nonencephalitogenic PLP-specific T cell c lone can induce autoimmune disease when expressed appropriately in vivo.