Role of individual T-cell epitopes of Theiler's virus in the pathogenesis of demyelination correlates with the ability to induce a Th1 response.
Intracerebral inoculation of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelination. Three major T-cell epitopes have previously been identified within the VP1 (VP1233-250), VP2 (VP274-86), and VP3 (VP324-37) capsid proteins in virus-infected SJL/J mice. These epitopes appear to account for the majority ( approximately 90%) of major histocompatibility complex class II-restricted T-cell responses to TMEV. Interestingly, the effect of immunization with synthetic peptides bearing the predominant T-cell epitopes on the course of TMEV-induced demyelination indicates that T cells reactive to the VP1 and VP2 epitopes, but not VP3, accelerate the pathogenesis of demyelination. The predominant pathogenic role of the T cells is verified by similar immunization with the fusion proteins containing the entire individual capsid proteins. The order of appearance and level of T cells specific for the individual epitopes during the course of demyelination are similar to each other. However, cytokine profiles of T cells from virus-infected mice indicate that T cells specific for the VP1 (and perhaps the VP2) epitope are Th1, whereas T cells reactive to VP3 are primarily Th2. These results suggest that Th1-type cells specific for VP1 and VP2 are involved in the pathogenesis of viral demyelination induced by TMEV. Thus, a predominance of Th1-inducing viral epitopes is likely critical for the pathogenesis of demyelination.
Yauch
R L
RL
Departments of Microbiology-Immunology and Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Palma
J P
JP
Yahikozawa
H
H
Koh
C S
CS
Kim
B S
BS
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002213:Capsid / Q000276:immunology; D003711:Demyelinating Diseases / Q000209:etiology*; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D017945:Theilovirus / Q000276:immunology*
D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments