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J Virol, July 1998, p. 6169-6174, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Role of Individual T-Cell Epitopes of Theiler's
Virus in the Pathogenesis of Demyelination Correlates with
the Ability To Induce a Th1 Response
Robert L.
Yauch,1,
JoAnn P.
Palma,1
Hiroyuki
Yahikozawa,1,2
Chang-Sung
Koh,2 and
Byung S.
Kim1,*
Departments of Microbiology-Immunology and Pathology,
Northwestern University Medical School, Chicago, Illinois
60611,1 and
Department of Medicine
(Neurology), Shinshu University Medical School, Matsumoto 390, Japan2
Received 20 January 1998/Accepted 2 April 1998
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 (~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.
*
Corresponding author. Mailing address: Department of
Microbiology-Immunology, Northwestern University Medical School, 303 East Chicago Ave., Chicago, IL 60611. Phone: (312) 503-8693. Fax: (312)
503-1339. E-mail: bskim{at}nwu.edu.

Present address: Division of Tumor Virology, Dana-Farber Cancer
Center, Boston, MA 02115.
J Virol, July 1998, p. 6169-6174, Vol. 72, No. 7
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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