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

Cross-reactivity of murine and recently human [CD8.sup.+] 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 th...

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Bibliographic Details
Published inThe Journal of clinical investigation Vol. 118; no. 3; pp. 1143 - 1153
Main Authors Kasprowicz, Victoria, Ward, Scott M, Turner, Alison, Grammatikos, Alexandros, Nolan, Brian E, Lewis-Ximenez, Lia, Sharp, Charles, Woodruff, Jenny, Fleming, Vicki M, Sims, Stuart, Walker, Bruce D, Sewell, Andrew K, Lauer, Georg M, Klenerman, Paul
Format Journal Article
LanguageEnglish
Published American Society for Clinical Investigation 01.03.2008
Subjects
Health aspects
Hepatitis C virus
Influenza viruses
T cells
United Kingdom
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Summary:Cross-reactivity of murine and recently human [CD8.sup.+] 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.sup.+] 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.sup.+] 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.sup.+] donors who showed strong HCV-NS3-specific reactivity. The Flu-NA peptide was a weak agonist for [CD8.sup.+] T cells in [HCV.sup.+] 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.
ISSN:0021-9738