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Journal of Virology, December 2008, p. 11734-11741, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.00435-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Lymphocytic Choriomeningitis Virus Infection Yields Overlapping CD4⁺ and CD8⁺ T-Cell Responses

Courtney Dow,^1,2 Carla Oseroff,¹ Bjoern Peters,¹ Courtney Nance-Sotelo,² John Sidney,¹ Michael Buchmeier,³ Alessandro Sette,¹ and Bianca R. Mothé^2*

The La Jolla Institute for Allergy and Immunology, La Jolla, California 92037,¹ Department of Biological Sciences, California State University, San Marcos, California 92096,² The Scripps Research Institute, La Jolla, California 92037³

Received 27 February 2008/ Accepted 2 September 2008

Activation of CD4⁺ T cells helps establish and sustain other immune responses. We have previously shown that responses against a broad set of nine CD4⁺ T-cell epitopes were present in the setting of lymphocytic choriomeningitis virus (LCMV) Armstrong infection in the context of H-2^d. This is quite disparate to the H-2^b setting, where only two epitopes have been identified. We were interested in determining whether a broad set of responses was unique to H-2^d or whether additional CD4⁺ T-cell epitopes could be identified in the setting of the H-2^b background. To pursue this question, we infected C57BL/6 mice with LCMV Armstrong and determined the repertoire of CD4⁺ T-cell responses using overlapping 15-mer peptides corresponding to the LCMV Armstrong sequence. We confirmed positive responses by intracellular cytokine staining and major histocompatibility complex (MHC)-peptide binding assays. A broad repertoire of responses was identified, consisting of six epitopes. These epitopes originate from the nucleoprotein (NP) and glycoprotein (GP). Out of the six newly identified CD4⁺ epitopes, four of them also stimulate CD8⁺ T cells in a statistically significant manner. Furthermore, we assessed these CD4⁺ T-cell responses during the memory phase of LCMV Armstrong infection and after infection with a chronic strain of LCMV and determined that a subset of the responses could be detected under these different conditions. This is the first example of a broad repertoire of shared epitopes between CD4⁺ and CD8⁺ T cells in the context of viral infection. These findings demonstrate that immunodominance is a complex phenomenon in the context of helper responses.

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* Corresponding author. Mailing address: Department of Biological Sciences, California State University, San Marcos, CA 92096. Phone: (760) 750-4637. Fax: (760) 750-3063. E-mail: bmothe{at}csusm.edu

Published ahead of print on 1 October 2008.

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Journal of Virology, December 2008, p. 11734-11741, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.00435-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.