Multiple sclerosis1 (MS) is an immune-mediated autoimmune
demyelinating disease in humans. The initiating event in MS is unknown, but epidemiological evidence suggests that
virus infections may be important and one possible mechanism for induction of
infection-induced
autoimmune disease is molecular mimicry. To test the ability of a virus encoding a self myelin mimic
epitope to induce an autoimmune response, we have developed a mouse model wherein the immunodominant myelin
epitope PLP139-151, or mimics of this
epitope, were inserted into a nonpathogenic variant of Theiler's murine encephalomyelitis virus (TMEV). SJL mice infected with TMEV containing PLP139-151 or a mimic of PLP139-151 expressed by the
protease IV protein of Haemophilus influenzae, sharing only 6/13
amino acids with the native
epitope, developed an early-onset
demyelinating disease associated with activation of CD4+ T cells reactive with PLP139-151. We have used this molecular mimicry model to further address the requirements for mimic
epitope processing and presentation during
infection and the requirements for TCR recognition and MHC binding of mimic
epitopes. We have also investigated whether molecular mimicry may require multiple
infections, with either the mimic-encoding virus or an unrelated virus, to initiate
autoimmune disease. Finally, we have asked whether a virus encoding a molecular mimic has to directly infect the target organ to induce
autoimmune disease. Overall, this virus-induced molecular mimicry model has provided critical information regarding the mechanisms by which
infection-induced molecular mimicry can induce
autoimmune diseases.