CD8+ T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph

Luca Hensen; Patricia T. Illing; E. Bridie Clemens; Thi H.O. Nguyen; Marios Koutsakos; Carolien E. van de Sandt; Nicole A. Mifsud; Andrea T. Nguyen; Christopher Szeto; Brendon Y. Chua; Hanim Halim; Simone Rizzetto; Fabio Luciani; Liyen Loh; Emma J. Grant; Phillipa M. Saunders; Andrew G. Brooks; Steve Rockman; Tom C. Kotsimbos; Allen C. Cheng; Michael Richards; Glen P. Westall; Linda M. Wakim; Thomas Loudovaris; Stuart I. Mannering; Michael Elliott; Stuart G. Tangye; David C. Jackson; Katie L. Flanagan; Jamie Rossjohn; Stephanie Gras; Jane Davies; Adrian Miller; Steven Y.C. Tong; Anthony W. Purcell; Katherine Kedzierska

doi:10.1038/s41467-021-23212-x

CD8⁺ T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph

Luca Hensen, Patricia T. Illing, E. Bridie Clemens, Thi H.O. Nguyen, Marios Koutsakos, Carolien E. van de Sandt, Nicole A. Mifsud, Andrea T. Nguyen, Christopher Szeto, Brendon Y. Chua, Hanim Halim, Simone Rizzetto, Fabio Luciani, Liyen Loh, Emma J. Grant, Phillipa M. Saunders, Andrew G. Brooks, Steve Rockman, Tom C. Kotsimbos, Allen C. ChengMichael Richards, Glen P. Westall, Linda M. Wakim, Thomas Loudovaris, Stuart I. Mannering, Michael Elliott, Stuart G. Tangye, David C. Jackson, Katie L. Flanagan, Jamie Rossjohn, Stephanie Gras, Jane Davies, Adrian Miller, Steven Y.C. Tong, Anthony W. Purcell, Katherine Kedzierska

Research output: Contribution to journal › Article › Research › peer-review

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Abstract

Indigenous people worldwide are at high risk of developing severe influenza disease. HLA-A*24:02 allele, highly prevalent in Indigenous populations, is associated with influenza-induced mortality, although the basis for this association is unclear. Here, we define CD8⁺ T-cell immune landscapes against influenza A (IAV) and B (IBV) viruses in HLA-A*24:02-expressing Indigenous and non-Indigenous individuals, human tissues, influenza-infected patients and HLA-A*24:02-transgenic mice. We identify immunodominant protective CD8⁺ T-cell epitopes, one towards IAV and six towards IBV, with A24/PB2_550–558-specific CD8⁺ T cells being cross-reactive between IAV and IBV. Memory CD8⁺ T cells towards these specificities are present in blood (CD27⁺CD45RA⁻ phenotype) and tissues (CD103⁺CD69⁺ phenotype) of healthy individuals, and effector CD27⁻CD45RA⁻PD-1⁺CD38⁺CD8⁺ T cells in IAV/IBV patients. Our data show influenza-specific CD8⁺ T-cell responses in Indigenous Australians, and advocate for T-cell-mediated vaccines that target and boost the breadth of IAV/IBV-specific CD8⁺ T cells to protect high-risk HLA-A*24:02-expressing Indigenous and non-Indigenous populations from severe influenza disease.

Original language	English
Article number	2931
Number of pages	20
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-23212-x
Publication status	Published - 18 May 2021

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10.1038/s41467-021-23212-xLicence: CC BY

Cite this

Hensen, L., Illing, P. T., Bridie Clemens, E., Nguyen, T. H. O., Koutsakos, M., van de Sandt, C. E., Mifsud, N. A., Nguyen, A. T., Szeto, C., Chua, B. Y., Halim, H., Rizzetto, S., Luciani, F., Loh, L., Grant, E. J., Saunders, P. M., Brooks, A. G., Rockman, S., Kotsimbos, T. C., ... Kedzierska, K. (2021). CD8⁺ T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph. Nature Communications, 12(1), Article 2931. https://doi.org/10.1038/s41467-021-23212-x

@article{d46e5d91e4d54ea9b97d710e42e8fde5,

title = "CD8+ T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph",

abstract = "Indigenous people worldwide are at high risk of developing severe influenza disease. HLA-A*24:02 allele, highly prevalent in Indigenous populations, is associated with influenza-induced mortality, although the basis for this association is unclear. Here, we define CD8+ T-cell immune landscapes against influenza A (IAV) and B (IBV) viruses in HLA-A*24:02-expressing Indigenous and non-Indigenous individuals, human tissues, influenza-infected patients and HLA-A*24:02-transgenic mice. We identify immunodominant protective CD8+ T-cell epitopes, one towards IAV and six towards IBV, with A24/PB2550–558-specific CD8+ T cells being cross-reactive between IAV and IBV. Memory CD8+ T cells towards these specificities are present in blood (CD27+CD45RA− phenotype) and tissues (CD103+CD69+ phenotype) of healthy individuals, and effector CD27−CD45RA−PD-1+CD38+CD8+ T cells in IAV/IBV patients. Our data show influenza-specific CD8+ T-cell responses in Indigenous Australians, and advocate for T-cell-mediated vaccines that target and boost the breadth of IAV/IBV-specific CD8+ T cells to protect high-risk HLA-A*24:02-expressing Indigenous and non-Indigenous populations from severe influenza disease.",

author = "Luca Hensen and Illing, {Patricia T.} and {Bridie Clemens}, E. and Nguyen, {Thi H.O.} and Marios Koutsakos and {van de Sandt}, {Carolien E.} and Mifsud, {Nicole A.} and Nguyen, {Andrea T.} and Christopher Szeto and Chua, {Brendon Y.} and Hanim Halim and Simone Rizzetto and Fabio Luciani and Liyen Loh and Grant, {Emma J.} and Saunders, {Phillipa M.} and Brooks, {Andrew G.} and Steve Rockman and Kotsimbos, {Tom C.} and Cheng, {Allen C.} and Michael Richards and Westall, {Glen P.} and Wakim, {Linda M.} and Thomas Loudovaris and Mannering, {Stuart I.} and Michael Elliott and Tangye, {Stuart G.} and Jackson, {David C.} and Flanagan, {Katie L.} and Jamie Rossjohn and Stephanie Gras and Jane Davies and Adrian Miller and Tong, {Steven Y.C.} and Purcell, {Anthony W.} and Katherine Kedzierska",

note = "Funding Information: HHD-A24 transgenic HHD mice were developed by Dr. Francoi{\c s} Lemonnier (Pasteur Institute, Paris, France). We thank the Monash Macromolecular Crystallization Facility staff and the staff at the Australian synchrotron for technical assistance. This research was undertaken in part using the MX2 beamline at the Australian Synchrotron, part of ANSTO, and made use of the Australian Cancer Research Foundation (ACRF) detector. The Australian National Health and Medical Research Council (NHMRC) Program Grant (#1071916) to K.K., NHMRC Project Grant (#1122524) to K.K., S.T., A.M., S.G., and A.W.P., and NHMRC Investigator Grant (#1173871) to K.K. supported this work. This work was also supported by NIAID UO1 grant 1U01AI144616-01; Dissection of Influenza Vaccination and Infection for Childhood Immunity (DIVINCI) to K.K. and by the ARC grant # DP190103282 to K.K., A.G.B., and L.L. L.H. was a recipient of Melbourne International Research Scholarship and Melbourne International Fee Remission Scholarship. C.E.S. had received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation program under the Marie Sk{\l}odowska-Curie grant agreement (#792532). J.R. is supported by an ARC Laureate fellowship. S.G. is an NHMRC SRF-A Fellow (#1159272). E.B.C. is NHMRC Peter Doherty Fellow. A.W.P. is supported by an NHMRC Principal Research Fellowship (#1137739) and NHMRC Project grant (#1085018) to A.W.P., N.A.M., and T.C.K. S.T. is an NHMRC Career Development Fellow (#1145033). E.J.G. is an NHMRC CJ Martin Fellow. P.T.I. was supported by an NHMRC Early Career Fellowship (#1072159) and Monash University Faculty of Medicine, Nursing and Health Sciences Senior Postdoctoral Fellowship (2020). Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = may,

day = "18",

doi = "10.1038/s41467-021-23212-x",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Hensen, L, Illing, PT, Bridie Clemens, E, Nguyen, THO, Koutsakos, M, van de Sandt, CE, Mifsud, NA, Nguyen, AT, Szeto, C, Chua, BY, Halim, H, Rizzetto, S, Luciani, F, Loh, L, Grant, EJ, Saunders, PM, Brooks, AG, Rockman, S, Kotsimbos, TC , Cheng, AC, Richards, M, Westall, GP, Wakim, LM, Loudovaris, T, Mannering, SI, Elliott, M, Tangye, SG, Jackson, DC, Flanagan, KL, Rossjohn, J , Gras, S, Davies, J, Miller, A, Tong, SYC, Purcell, AW & Kedzierska, K 2021, 'CD8⁺ T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph', Nature Communications, vol. 12, no. 1, 2931. https://doi.org/10.1038/s41467-021-23212-x

TY - JOUR

T1 - CD8+ T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph

AU - Hensen, Luca

AU - Illing, Patricia T.

AU - Bridie Clemens, E.

AU - Nguyen, Thi H.O.

AU - Koutsakos, Marios

AU - van de Sandt, Carolien E.

AU - Mifsud, Nicole A.

AU - Nguyen, Andrea T.

AU - Szeto, Christopher

AU - Chua, Brendon Y.

AU - Halim, Hanim

AU - Rizzetto, Simone

AU - Luciani, Fabio

AU - Loh, Liyen

AU - Grant, Emma J.

AU - Saunders, Phillipa M.

AU - Brooks, Andrew G.

AU - Rockman, Steve

AU - Kotsimbos, Tom C.

AU - Cheng, Allen C.

AU - Richards, Michael

AU - Westall, Glen P.

AU - Wakim, Linda M.

AU - Loudovaris, Thomas

AU - Mannering, Stuart I.

AU - Elliott, Michael

AU - Tangye, Stuart G.

AU - Jackson, David C.

AU - Flanagan, Katie L.

AU - Rossjohn, Jamie

AU - Gras, Stephanie

AU - Davies, Jane

AU - Miller, Adrian

AU - Tong, Steven Y.C.

AU - Purcell, Anthony W.

AU - Kedzierska, Katherine

N1 - Funding Information: HHD-A24 transgenic HHD mice were developed by Dr. Francoiş Lemonnier (Pasteur Institute, Paris, France). We thank the Monash Macromolecular Crystallization Facility staff and the staff at the Australian synchrotron for technical assistance. This research was undertaken in part using the MX2 beamline at the Australian Synchrotron, part of ANSTO, and made use of the Australian Cancer Research Foundation (ACRF) detector. The Australian National Health and Medical Research Council (NHMRC) Program Grant (#1071916) to K.K., NHMRC Project Grant (#1122524) to K.K., S.T., A.M., S.G., and A.W.P., and NHMRC Investigator Grant (#1173871) to K.K. supported this work. This work was also supported by NIAID UO1 grant 1U01AI144616-01; Dissection of Influenza Vaccination and Infection for Childhood Immunity (DIVINCI) to K.K. and by the ARC grant # DP190103282 to K.K., A.G.B., and L.L. L.H. was a recipient of Melbourne International Research Scholarship and Melbourne International Fee Remission Scholarship. C.E.S. had received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement (#792532). J.R. is supported by an ARC Laureate fellowship. S.G. is an NHMRC SRF-A Fellow (#1159272). E.B.C. is NHMRC Peter Doherty Fellow. A.W.P. is supported by an NHMRC Principal Research Fellowship (#1137739) and NHMRC Project grant (#1085018) to A.W.P., N.A.M., and T.C.K. S.T. is an NHMRC Career Development Fellow (#1145033). E.J.G. is an NHMRC CJ Martin Fellow. P.T.I. was supported by an NHMRC Early Career Fellowship (#1072159) and Monash University Faculty of Medicine, Nursing and Health Sciences Senior Postdoctoral Fellowship (2020). Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/5/18

Y1 - 2021/5/18

N2 - Indigenous people worldwide are at high risk of developing severe influenza disease. HLA-A*24:02 allele, highly prevalent in Indigenous populations, is associated with influenza-induced mortality, although the basis for this association is unclear. Here, we define CD8+ T-cell immune landscapes against influenza A (IAV) and B (IBV) viruses in HLA-A*24:02-expressing Indigenous and non-Indigenous individuals, human tissues, influenza-infected patients and HLA-A*24:02-transgenic mice. We identify immunodominant protective CD8+ T-cell epitopes, one towards IAV and six towards IBV, with A24/PB2550–558-specific CD8+ T cells being cross-reactive between IAV and IBV. Memory CD8+ T cells towards these specificities are present in blood (CD27+CD45RA− phenotype) and tissues (CD103+CD69+ phenotype) of healthy individuals, and effector CD27−CD45RA−PD-1+CD38+CD8+ T cells in IAV/IBV patients. Our data show influenza-specific CD8+ T-cell responses in Indigenous Australians, and advocate for T-cell-mediated vaccines that target and boost the breadth of IAV/IBV-specific CD8+ T cells to protect high-risk HLA-A*24:02-expressing Indigenous and non-Indigenous populations from severe influenza disease.

AB - Indigenous people worldwide are at high risk of developing severe influenza disease. HLA-A*24:02 allele, highly prevalent in Indigenous populations, is associated with influenza-induced mortality, although the basis for this association is unclear. Here, we define CD8+ T-cell immune landscapes against influenza A (IAV) and B (IBV) viruses in HLA-A*24:02-expressing Indigenous and non-Indigenous individuals, human tissues, influenza-infected patients and HLA-A*24:02-transgenic mice. We identify immunodominant protective CD8+ T-cell epitopes, one towards IAV and six towards IBV, with A24/PB2550–558-specific CD8+ T cells being cross-reactive between IAV and IBV. Memory CD8+ T cells towards these specificities are present in blood (CD27+CD45RA− phenotype) and tissues (CD103+CD69+ phenotype) of healthy individuals, and effector CD27−CD45RA−PD-1+CD38+CD8+ T cells in IAV/IBV patients. Our data show influenza-specific CD8+ T-cell responses in Indigenous Australians, and advocate for T-cell-mediated vaccines that target and boost the breadth of IAV/IBV-specific CD8+ T cells to protect high-risk HLA-A*24:02-expressing Indigenous and non-Indigenous populations from severe influenza disease.

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U2 - 10.1038/s41467-021-23212-x

DO - 10.1038/s41467-021-23212-x

M3 - Article

C2 - 34006841

AN - SCOPUS:85106192753

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2931

ER -

CD8⁺ T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph

Abstract

UN SDGs

Access to Document

Other files and links

Understanding the complexity of antigen presentation

The role of cross-reactive T cells in severe lung disease following viral respiratory infections

Limiting the impact of influenza

Australian Synchrotron

Cite this

CD8+ T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph

Abstract

UN SDGs

Access to Document

Other files and links

Projects

Understanding the complexity of antigen presentation

The role of cross-reactive T cells in severe lung disease following viral respiratory infections

Limiting the impact of influenza

Equipment

Australian Synchrotron

Cite this

CD8⁺ T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph