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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 ^,

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-2^b mice. Although antigen-specific responses against LCMV infection are well studied, we found that a significant fraction of the CD8⁺ CD44^hi T-cell response to LCMV in H-2^b 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-) induction from CD8⁺ T cells derived from LCMV-infected H-2^b mice. We identified 19 novel epitopes. Together with the 9 previously known, these epitopes account for the total CD8⁺ CD44^hi response. Thus, bystander T-cell activation does not contribute appreciably to the CD8⁺ CD44^hi 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- 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.

Published ahead of print on 28 February 2007.

Kirin publication number 789.

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