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Journal of Virology, December 2008, p. 12205-12212, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01463-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The CD8 T-Cell Response against Murine Gammaherpesvirus 68 Is Directed toward a Broad Repertoire of Epitopes from both Early and Late Antigens {triangledown} ,{dagger}

Sara Gredmark-Russ, Evelyn J. Cheung, Marisa K. Isaacson, Hidde L. Ploegh,* and Gijsbert M. Grotenbreg{ddagger}

Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142

Received 12 July 2008/ Accepted 6 October 2008

Infection of mice with murine gammaherpesvirus 68 (MHV-68) robustly activates CD8 T cells, but only six class I major histocompatibility complex (MHC)-restricted epitopes have been described to date for the widely used H-2b haplotype mice. To explore the specificity and kinetics of the cytotoxic T-lymphocyte response in MHV-68-infected C57BL/6 mice, we screened for H-2Kb- and H-2Db-restricted epitopes using a set of 384 candidate epitopes in an MHC tetramer-based approach and identified 19 new epitopes in 16 different open reading frames. Of the six known H-2Kb- and H-2Db-restricted epitopes, we confirmed a response against three and did not detect CD8 T-cell-specific responses for the remaining three. The peak of the CD8 T-cell response to most peptides occurs between 6 and 10 days postinfection. The respective MHC tetramer-positive CD8 T cells display an activated/effector phenotype (CD62Llo and CD44hi) and produce gamma interferon upon peptide stimulation ex vivo. MHV-68 infection in vivo elicits a response to multiple viral epitopes, derived from both early and late viral antigens, illustrating a far broader T-cell repertoire and more-rapid activation than those previously recorded.

* Corresponding author. Mailing address: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142. Phone: (617) 324-1878. Fax: (617) 452-3566. E-mail: ploegh{at}wi.mit.edu

{triangledown} Published ahead of print on 15 October 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} Present address: Immunology Programme and Departments of Microbiology and Biological Sciences, National University of Singapore, Singapore.

Journal of Virology, December 2008, p. 12205-12212, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01463-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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