Viral Infection of Transgenic Mice Expressing a Viral Protein in Oligodendrocytes Leads to Chronic Central Nervous System Autoimmune Disease

Evans, Claire F.; Horwitz, Marc S.; Hobbs, Monte V.; Oldstone, Michael B.A.

(10). Specific peptides from herpes simplex, adeno-, human papilloma, Epstein-Barr, influenza, and reo-viruses were able to activate human MBP-specific T cell clones that had been established from peripheral blood lymphocytes of two multiple sclerosis (MS) patients. A peptide from the bacterium Pseudomonas aeruginosa was also able to activate one of the MBP-specific T cell clones. Activation of the MBPspecific T cell clones by as many as 3-4 different viral peptides indicated that a single TCR could recognize peptides from several unrelated sources, and this recognition resulted in T cell activation. In other studies, T cell lines established from MS patients were reactive to both MBP and a sequence from the human respiratory coronavirus 229E (11, 34) . Additionally, molecular mimicry between human transaldolase (TAL-H), which in the brain is expressed selectively in oligodendrocytes, and human T cell lymphotropic virus type I/human immunodeficiency virus type 1 gag proteins has also been described (12) . TAL-H stimulated proliferation of peripheral blood lymphocytes from patients with MS, and in addition, autoantibodies to TAL-H were detected in the serum and cerebrospinal fluid of these patients. Thus, molecular mimicry between viruses and oligodendrocyte proteins may be important in the etiology of a human CNS autoimmune disease such as MS.