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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
Victoria Kasprowicz, … , Georg M. Lauer, Paul Klenerman
Victoria Kasprowicz, … , Georg M. Lauer, Paul Klenerman
Published February 1, 2008
Citation Information: J Clin Invest. 2008;118(3):1143-1153. https://doi.org/10.1172/JCI33082.
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Research Article Immunology

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

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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.

Authors

Victoria Kasprowicz, Scott M. Ward, Alison Turner, Alexandros Grammatikos, Brian E. Nolan, Lia Lewis-Ximenez, Charles Sharp, Jenny Woodruff, Vicki M. Fleming, Stuart Sims, Bruce D. Walker, Andrew K. Sewell, Georg M. Lauer, Paul Klenerman

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