Since the encephalitogenic MBP peptides are known, the extent to which they are mimicked by proteins from other organisms can be assessed. For example, one MBP peptide (amino acid residues 61-69) is highly homologous with a peptide in the P3 protein of the measles virus (see Table 20-3). In one study, the sequence of another encephalitogenic MBP peptide (66-75) was compared with the known sequences of a large number of viral proteins. This computer analysis revealed sequence homologies between this MBP peptide and a number of peptides from animal viruses, including influenza, polyoma, adenovirus, Rous sarcoma, Abelson leukemia, poliomyelitis, Epstein-Barr, and hepatitis B viruses.
One peptide from the polymerase enzyme of the hepatitis B virus was particularly striking, exhibiting 60% homology with a sequence in the encephalitogenic MBP peptide. To test the hypothesis that molecular mimicry can generate autoimmunity, rabbits were immunized with this hepatitis B virus peptide. The peptide was shown to induce both the formation of antibody and the proliferation of T cells that cross-reacted with MBP; in addition, central nervous system tissue from the immunized rabbits showed cellular infiltration characteristic of EAE.
These findings suggest that infection with certain viruses expressing epitopes that mimic sequestered self-components, such as myelin basic protein, may induce autoimmunity to those components. Susceptibility to this type of autoimmunity may also be influenced by the MHC haplotype of the individual, since certain class I and class II MHC molecules may be more effective than others in presenting the homologous pep-tide for T-cell activation.
Another particularly compelling example of molecular mimicry comes from studies of herpes stromal keratinitis (HSK). In these studies, investigators showed that prior infection of mice with herpes simplex virus Type 1 leads to a disease known as herpes stromal keratinitis (HSK), an autoimmune-like disease in which T cells specific for a particular viral peptide attack corneal tissue, thus causing blindness. These data demonstrated very clearly that a particular epi-tope of HSV-1 is responsible for the disease and that mutant strains of HSV-1 that lack this epitope do not cause HSK. The data provide strong evidence for molecular mimicry in the development of a particular autoimmune disease.
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