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

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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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.