This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kotturi, M. F.
Right arrow Articles by Sette, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kotturi, M. F.
Right arrow Articles by Sette, A.

 Previous Article  |  Next Article 

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.




This article has been cited by other articles:

  • Yauch, L. E., Zellweger, R. M., Kotturi, M. F., Qutubuddin, A., Sidney, J., Peters, B., Prestwood, T. R., Sette, A., Shresta, S. (2009). A Protective Role for Dengue Virus-Specific CD8+ T Cells. J. Immunol. 182: 4865-4873 [Abstract] [Full Text]  
  • Thomsen, A. R. (2009). Lymphocytic Choriomeningitis Virus-Induced Central Nervous System Disease: a Model for Studying the Role of Chemokines in Regulating the Acute Antiviral CD8+ T-Cell Response in an Immune-Privileged Organ. J. Virol. 83: 20-28 [Full Text]  
  • Dow, C., Oseroff, C., Peters, B., Nance-Sotelo, C., Sidney, J., Buchmeier, M., Sette, A., Mothe, B. R. (2008). Lymphocytic Choriomeningitis Virus Infection Yields Overlapping CD4+ and CD8+ T-Cell Responses. J. Virol. 82: 11734-11741 [Abstract] [Full Text]  
  • Blackburn, S. D., Shin, H., Freeman, G. J., Wherry, E. J. (2008). Selective expansion of a subset of exhausted CD8 T cells by {alpha}PD-L1 blockade. Proc. Natl. Acad. Sci. USA 105: 15016-15021 [Abstract] [Full Text]  
  • Kotturi, M. F., Scott, I., Wolfe, T., Peters, B., Sidney, J., Cheroutre, H., von Herrath, M. G., Buchmeier, M. J., Grey, H., Sette, A. (2008). Naive Precursor Frequencies and MHC Binding Rather Than the Degree of Epitope Diversity Shape CD8+ T Cell Immunodominance. J. Immunol. 181: 2124-2133 [Abstract] [Full Text]  
  • Lin, S.-J., Chen, A. T., Welsh, R. M. (2008). Immune system derived from homeostatic proliferation generates normal CD8 T-cell memory but altered repertoires and diminished heterologous immune responses. Blood 112: 680-689 [Abstract] [Full Text]  
  • Chen, M., Lan, S., Ou, R., Price, G. E., Jiang, H., de la Torre, J. C., Moskophidis, D. (2008). Genomic and biological characterization of aggressive and docile strains of lymphocytic choriomeningitis virus rescued from a plasmid-based reverse-genetics system. J. Gen. Virol. 89: 1421-1433 [Abstract] [Full Text]  
  • Schildknecht, A., Welti, S., Geuking, M. B., Hangartner, L., van den Broek, M. (2008). Absence of CTL Responses to Early Viral Antigens Facilitates Viral Persistence. J. Immunol. 180: 3113-3121 [Abstract] [Full Text]  
  • Singh, A., Suresh, M. (2007). A role for TNF in limiting the duration of CTL effector phase and magnitude of CD8 T cell memory. J. Leukoc. Biol. 82: 1201-1211 [Abstract] [Full Text]  
  • Althaus, C. L., Ganusov, V. V., De Boer, R. J. (2007). Dynamics of CD8+ T Cell Responses during Acute and Chronic Lymphocytic Choriomeningitis Virus Infection. J. Immunol. 179: 2944-2951 [Abstract] [Full Text]