Protective Efficacy of Cross-Reactive CD8( ) T Cells Recognising Mutant Viral Epitopes Depends on Peptide-MHC-I Structural Interactions and T Cell Activation Threshold

Sophie A Valkenburg; Stephanie Gras; Carole Guillonneau; Nicole L La Gruta; Paul G Thomas; Anthony W Purcell; Jamie Rossjohn; Peter C Doherty; Stephen J Turner; Katherine Kedzierska

Journal article

Protective Efficacy of Cross-Reactive CD8( ) T Cells Recognising Mutant Viral Epitopes Depends on Peptide-MHC-I Structural Interactions and T Cell Activation Threshold

Sophie A Valkenburg, Stephanie Gras, Carole Guillonneau, Nicole L La Gruta, Paul G Thomas, Anthony W Purcell, Jamie Rossjohn, Peter C Doherty, Stephen J Turner, Katherine Kedzierska

PLOS PATHOGENS | PUBLIC LIBRARY SCIENCE | Published : 2010

DOI: 10.1371/journal.ppat.1001039

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Abstract

Emergence of a new influenza strain leads to a rapid global spread of the virus due to minimal antibody immunity. Pre-existing CD8(+) T-cell immunity directed towards conserved internal viral regions can greatly ameliorate the disease. However, mutational escape within the T cell epitopes is a substantial issue for virus control and vaccine design. Although mutations can result in a loss of T cell recognition, some variants generate cross-reactive T cell responses. In this study, we used reverse genetics to modify the influenza NP(336-374) peptide at a partially-solvent exposed residue (N->A, NPN3A mutation) to assess the availability, effectiveness and mechanism underlying influenza-specifi..

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University of Melbourne Researchers

Jamie Rossjohn Author Microbiology and Immunology

Peter Doherty Author Microbiology and Immunology

Katherine Kedzierska Author Microbiology and Immunology

Sophie Valkenburg Author Microbiology and Immunology

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Funding Acknowledgements

This work was funded by the NHMRC Project Grants to PCD (AI454595) and KK (AI454312), a University of Melbourne Early Career Researcher Grant (to KK), NIH grant AI170251 and NHMRC program grant to PCD, SJT (AI567122). KK and NLG are NHMRC RD Wright Fellows, AWP is a NHMRC Senior Research Fellow, SJT is a Pfizer Senior Research Fellow and CG is a Marie Curie International Fellow and is supported by the 6th FP of the EU, Marie Curie #040840. JR is an ARC Federation Fellow. SAV is a recipient of the Australian Postgraduate Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.