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Journal of Virology, May 1999, p. 3702-3708, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Prevalent Class I-Restricted T-Cell Response to the Theiler's Virus Epitope Db:VP2121-130 in the Absence of Endogenous CD4 Help, Tumor Necrosis Factor Alpha, Gamma Interferon, Perforin, or Costimulation through CD28

Aaron J. Johnson,1 M. Kariuki Njenga,2 Michael J. Hansen,1 Scott T. Kuhns,1 Lieping Chen,1 Moses Rodriguez,2 and Larry R. Pease1,*

Departments of Immunology1 and Neurology,2 Mayo Clinic and Foundation, Rochester, Minnesota 55905

Received 6 November 1998/Accepted 21 January 1999

C57BL/6 mice mount a cytotoxic T-lymphocyte (CTL) response against the Daniel's strain of Theiler's murine encephalomyelitis virus (TMEV) 7 days after infection and do not develop persistent infection or the demyelinating syndrome similar to multiple sclerosis seen in susceptible mice. The TMEV capsid peptide VP2121-130 sensitizes H-2Db+ target cells for killing by central-nervous-system-infiltrating lymphocytes (CNS-ILs) isolated from C57BL/6 mice infected intracranially. Db:VP2121-130 peptide tetramers were used to stain CD8+ CNS-ILs, revealing that 50 to 63% of these cells bear receptors specific for VP2121-130 presented in the context of Db. No T cells bearing this specificity were found in the cervical lymph nodes or spleens of TMEV-infected mice. H-2b mice lacking CD4, class II, gamma interferon, or CD28 expression are susceptible to persistent virus infection but surprisingly still generate high frequencies of CD8+, Db:VP2121-130-specific T cells. However, CD4-negative mice generate a lower frequency of Db:VP2121-130-specific T cells than do class II negative or normal H-2b animals. Resistant tumor necrosis factor alpha receptor I knockout mice also generate a high frequency of CD8+ CNS-ILs specific for Db:VP2121-130. Furthermore, normally susceptible FVB mice that express a Db transgene generate Db:VP2121-130-specific CD8+ CNS-ILs at a frequency similar to that of C57BL/6 mice. These results demonstrate that VP2121-130 presented in the context of Db is an immunodominant epitope in TMEV infection and that the frequency of the VP2121-130-specific CTLs appears to be independent of several key inflammatory mediators and genetic background but is regulated in part by the expression of CD4.

* Corresponding author. Mailing address: Mayo Clinic, 200 First St. SW, Rochester, MN 55905. Phone: (507) 284-8177. Fax: (507) 266-0981. E-mail: pease.larry{at}mayo.edu.

Journal of Virology, May 1999, p. 3702-3708, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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