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Journal of Virology, May 2007, p. 4928-4940, Vol. 81, No. 10
0022-538X/07/$08.00+0     doi:10.1128/JVI.02632-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The CD8+ T-Cell Response to Lymphocytic Choriomeningitis Virus Involves the L Antigen: Uncovering New Tricks for an Old Virus{triangledown} ,{dagger}

Maya F. Kotturi,1 Bjoern Peters,1 Fernando Buendia-Laysa Jr.,1 John Sidney,1 Carla Oseroff,1 Jason Botten,2 Howard Grey,1 Michael J. Buchmeier,2 and Alessandro Sette1*

Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037,1 Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 920372

Received 28 November 2006/ Accepted 14 February 2007

CD8+ T-cell responses control lymphocytic choriomeningitis virus (LCMV) infection in H-2b mice. Although antigen-specific responses against LCMV infection are well studied, we found that a significant fraction of the CD8+ CD44hi T-cell response to LCMV in H-2b mice was not accounted for by known epitopes. We screened peptides predicted to bind major histocompatibility complex class I and overlapping 15-mer peptides spanning the complete LCMV proteome for gamma interferon (IFN-{gamma}) induction from CD8+ T cells derived from LCMV-infected H-2b mice. We identified 19 novel epitopes. Together with the 9 previously known, these epitopes account for the total CD8+ CD44hi response. Thus, bystander T-cell activation does not contribute appreciably to the CD8+ CD44hi pool. Strikingly, 15 of the 19 new epitopes were derived from the viral L polymerase, which, until now, was not recognized as a target of the cellular response induced by LCMV infection. The L epitopes induced significant levels of in vivo cytotoxicity and conferred protection against LCMV challenge. Interestingly, protection from viral challenge was best correlated with the cytolytic potential of CD8+ T cells, whereas IFN-{gamma} production and peptide avidity appear to play a lesser role. Taken together, these findings illustrate that the LCMV-specific CD8+ T-cell response is more complex than previously appreciated.

* Corresponding author. Mailing address: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037. Phone: (858) 752-6916. Fax: (858) 752-6985. E-mail: alex{at}liai.org

{triangledown} Published ahead of print on 28 February 2007.

{dagger} Kirin publication number 789.

Journal of Virology, May 2007, p. 4928-4940, Vol. 81, No. 10
0022-538X/07/$08.00+0     doi:10.1128/JVI.02632-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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