Challenging immunodominance of influenza-specific CD8( ) T cell responses restricted by the risk-associated HLA-A*68:01 allomorph

CE van de Sandt; EB Clemens; EJ Grant; LC Rowntree; S Sant; H Halim; J Crowe; AC Cheng; TC Kotsimbos; M Richards; A Miller; SYC Tong; J Rossjohn; THO Nguyen; S Gras; W Chen; K Kedzierska

Journal article

Challenging immunodominance of influenza-specific CD8( ) T cell responses restricted by the risk-associated HLA-A*68:01 allomorph

CE van de Sandt, EB Clemens, EJ Grant, LC Rowntree, S Sant, H Halim, J Crowe, AC Cheng, TC Kotsimbos, M Richards, A Miller, SYC Tong, J Rossjohn, THO Nguyen, S Gras, W Chen, K Kedzierska

NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2019

DOI: 10.1038/s41467-019-13346-4

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Abstract

Although influenza viruses lead to severe illness in high-risk populations, host genetic factors associated with severe disease are largely unknown. As the HLA-A*68:01 allele can be linked to severe pandemic 2009-H1N1 disease, we investigate a potential impairment of HLA-A*68:01-restricted CD8+ T cells to mount robust responses. We elucidate the HLA-A*68:01+CD8+ T cell response directed toward an extended influenza-derived nucleoprotein (NP) peptide and show that only ~35% individuals have immunodominant A68/NP145+CD8+ T cell responses. Dissecting A68/NP145+CD8+ T cells in low vs. medium/high responders reveals that high responding donors have A68/NP145+CD8+ memory T cells with clonally expa..

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University of Melbourne Researchers

Steven Tong Author Infectious Diseases

Michael Richards Author Infectious Diseases

Louise Rowntree Author Microbiology and Immunology

Bridie Clemens Author Microbiology and Immunology

Oanh Nguyen Author Microbiology and Immunology

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Grants

Awarded by NHMRC

Awarded by European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant

Awarded by ARC Australian Laureate Fellowship

Funding Acknowledgements

This work has been supported by a NHMRC Program Grant #1071916 to K.K. and a NHMRC Project Grant #1122524 to K.K., S.T., A.M., and S.G. C.E.S. has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 792532 and University of Melbourne McKenzie Fellowship laboratory support. E.B.C. is supported by an NHMRC Peter Doherty Fellowship (#1091516). K.K. is supported by a NHMRC Senior Research Fellowship Level B (GNT#1102792). S.G. is supported by a NHMRC Senior Research Fellowship (GNT#1159272). E.J.G. is supported by an Early Career NHMRC CJ Martin Fellowship. J.R. is supported by an ARC Australian Laureate Fellowship (GNT#1110429). Authors wish to thank Dr Lucy Sullivan for providing samples to this study.