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Journal of Virology, March 2007, p. 2307-2317, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.02063-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

HLA-A2-Restricted Protection against Lethal Lymphocytic Choriomeningitis{triangledown} ,{dagger}

Jason Botten,1* J. Lindsay Whitton,1 Polly Barrowman,1 John Sidney,2 Jason K. Whitmire,1 Jeff Alexander,3 Joey P. C. Ting,1 Huynh-Hoa Bui,2 Alessandro Sette,2 and Michael J. Buchmeier1

Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037,1 La Jolla Institute of Allergy and Immunology, La Jolla, California 92121,2 Pharmexa-Epimmune, San Diego, California 921213

Received 20 September 2006/ Accepted 1 December 2006

The consequences of human lymphocytic choriomeningitis virus (LCMV) infection can be severe, including aseptic meningitis in immunocompetent individuals, hydrocephalus or chorioretinitis in fetal infection, or a highly lethal outcome in immunosuppressed individuals. In murine models of LCMV infection, CD8+ T cells play a primary role in providing protective immunity, and there is evidence that cellular immunity may also be important in related arenavirus infections in humans. For this reason, we sought to identify HLA-A2 supertype-restricted epitopes from the LCMV proteome and evaluate them as vaccine determinants in HLA transgenic mice. We identified four HLA-A*0201-restricted peptides—nucleoprotein NP69-77, glycoprotein precursor GPC10-18, GPC447-455, and zinc-binding protein Z49-58—that displayed high-affinity binding (≤275 nM) to HLA-A*0201, induced CD8+ T-cell responses of high functional avidity in HLA-A*0201 transgenic mice, and were naturally processed from native LCMV antigens in HLA-restricted human antigen presenting cells. One of the epitopes (GPC447-455), after peptide immunization of HLA-A*0201 mice, induced CD8+ T cells capable of killing peptide-pulsed HLA-A*0201-restricted target cells in vivo and protected mice against lethal intracranial challenge with LCMV.

* Corresponding author. Mailing address: Molecular and Integrative Neurosciences Department, The Scripps Research Institute, SP30-2020, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-7162. Fax: (858) 784-7369. E-mail: jbotten{at}scripps.edu.

{triangledown} Published ahead of print on 13 December 2006.

{dagger} TSRI manuscript 18473-MIND.

Journal of Virology, March 2007, p. 2307-2317, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.02063-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Assarsson, E., Sidney, J., Oseroff, C., Pasquetto, V., Bui, H.-H., Frahm, N., Brander, C., Peters, B., Grey, H., Sette, A. (2007). A Quantitative Analysis of the Variables Affecting the Repertoire of T Cell Specificities Recognized after Vaccinia Virus Infection. J. Immunol. 178: 7890-7901 [Abstract] [Full Text]  
  • Kotturi, M. F., Peters, B., Buendia-Laysa, F. Jr., Sidney, J., Oseroff, C., Botten, J., Grey, H., Buchmeier, M. J., Sette, A. (2007). The CD8+ T-Cell Response to Lymphocytic Choriomeningitis Virus Involves the L Antigen: Uncovering New Tricks for an Old Virus. J. Virol. 81: 4928-4940 [Abstract] [Full Text]  


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