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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
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Affilliation
Partners AIDS Research Center and Infectious Disease Division. Massachusetts General Hospital and Harvard Medical School. Charlestown, Massachusetts, USA.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Partners AIDS Research Center and Infectious Disease Division. Massachusetts General Hospital and Harvard Medical School. Charlestown, Massachusetts, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Virologia. Rio de Janeiro, RJ. Brasil.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Partners AIDS Research Center and Infectious Disease Division. Massachusetts General Hospital and Harvard Medical School. Charlestown, Massachusetts, USA.
University of Cardiff. Department of Medical Biochemistry and Immunology. Cardiff, United Kingdom.
Partners AIDS Research Center and Infectious Disease Division. Massachusetts General Hospital and Harvard Medical School. Charlestown, Massachusetts, USA.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Partners AIDS Research Center and Infectious Disease Division. Massachusetts General Hospital and Harvard Medical School. Charlestown, Massachusetts, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Virologia. Rio de Janeiro, RJ. Brasil.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
Partners AIDS Research Center and Infectious Disease Division. Massachusetts General Hospital and Harvard Medical School. Charlestown, Massachusetts, USA.
University of Cardiff. Department of Medical Biochemistry and Immunology. Cardiff, United Kingdom.
Partners AIDS Research Center and Infectious Disease Division. Massachusetts General Hospital and Harvard Medical School. Charlestown, Massachusetts, USA.
Peter Medawar Building for Pathogen Research. Nuffield Department of Clinical Medicine. University of Oxford. Oxford, United Kingdom.
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.
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