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The Memory T Cell Response to West Nile Virus in Symptomatic Humans following Natural Infection Is Not Influenced by Age and Is Dominated by a Restricted Set of CD8⁺ T Cell Epitopes¹

Robin Parsons^*, Alina Lelic^*, Lisa Hayes^*, Alexandra Carter^*, Laura Marshall^*, Carole Evelegh^*, Michael Drebot, Maya Andonova, Curtis McMurtrey, William Hildebrand, Mark B. Loeb^* and Jonathan L. Bramson^2,*

^* Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada; and Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104

We examined the West Nile virus (WNV)-specific T cell response in a cohort of 52 patients with symptomatic WNV infections, including neuroinvasive and non-invasive disease. Although all virus proteins were shown to contain T cell epitopes, certain proteins, such as E, were more commonly targeted by the T cell response. Most patients exhibited reactivity toward 3–4 individual WNV peptides; however, several patients exhibited reactivity toward >10 individual peptides. The relative hierarchy of T cell reactivities in all patients showed a fixed pattern that was sustained throughout the 12-mo period of the current study. Surprisingly, we did not observe any relationship between age and either the breadth or magnitude of the T cell response following infection. We also did not observe a relationship between disease severity and either the breadth or magnitude of the T cell response. The T cell epitopes were distributed in a non-random fashion across the viral polyprotein and a limited number of epitopes appeared to dominate the CD8⁺ T cell response within our cohort. These data provide important new insight into the T cell response against WNV in humans.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Contracts N01-AI-40066 (to J.L.B. and M.B.L.) and HHSN266200400027C (to W.H.H.). J.L.B. and M.L. were supported by an Rx & D-Health Research Foundation/Canadian Institutes of Health Research Career Award in Health Research and a Canadian Institutes of Health Research New Investigator Award, respectively.

² Address correspondence and reprint requests to Dr. Jonathan Bramson, Department of Pathology and Molecular Medicine, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada, L8N 3Z5. E-mail address: bramsonj{at}mcmaster.ca

³ Abbreviations used in this paper: WNV, West Nile virus; cRPMI, complete RPMI 1640; SFC, spot forming cell.