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Defining the directionality and quality of influenza virus-specific CD8+ T cell cross-reactivity in individuals infected with hepatitis C virus

Kasprowicz, Victoria, Ward, Scott M., Turner, Alison, Grammatikos, Alexandros, Nolan, Brian E., Lewis-Ximenez, Lia, Sharp, Charles, Woodfruff, Jenny, Fleming, Vicki M., Sims, Stuart, Walker, Bruce D., Sewell, Andrew K., Lauer, Georg M. and Klenerman, Paul 2008. Defining the directionality and quality of influenza virus-specific CD8+ T cell cross-reactivity in individuals infected with hepatitis C virus. Journal of Clinical Investigation 118 (3) , pp. 1143-1153. 10.1172/JCI33082

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Abstract

Cross-reactivity of murine and recently human CD8+ T cells between different viral peptides, i.e., heterologous immunity, has been well characterized. However, the directionality and quality of these cross-reactions is critical in determining their biological importance. Herein we analyzed the response of human CD8+ T cells that recognize both a hepatitis C virus peptide (HCV-NS3) and a peptide derived from the influenza neuraminidase protein (Flu-NA). To detect the cross-reactive CD8+ T cells, we used peptide-MHC class I complexes (pMHCs) containing a new mutant form of MHC class I able to bind CD8 more strongly than normal MHC class I complexes. T cell responses against HCV-NS3 and Flu-NA peptide were undetectable in normal donors. In contrast, some responses against the Flu-NA peptide were identified in HCV+ donors who showed strong HCV-NS3–specific reactivity. The Flu-NA peptide was a weak agonist for CD8+ T cells in HCV+ individuals on the basis of novel pMHCs and functional assays. These data support the idea of cross-reactivity between the 2 peptides, but indicate that reactivity toward the Flu-NA peptide is highly CD8-dependent and occurs predominantly after priming during HCV infection. Our findings indicate the utility of the novel pMHCs in dissecting cross-reactivity and suggest that cross-reactivity between HCV and influenza is relatively weak. Further studies are needed to relate affinity and functionality of cross-reactive T cells.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology
R Medicine > R Medicine (General)
R Medicine > RA Public aspects of medicine
R Medicine > RC Internal medicine
Additional Information: Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/0021-9738/ (accessed 24/02/2014)
Publisher: American Society for Clinical Investigation
ISSN: 0021-9738
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 03:53
URI: http://orca-mwe.cf.ac.uk/id/eprint/28636

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