@article{9038a3ff82784267879c9eee044933ea,
title = "CD8+ T-cell responses towards conserved influenza B virus epitopes across anatomical sites and age",
abstract = "Influenza B viruses (IBVs) cause substantive morbidity and mortality, and yet immunity towards IBVs remains understudied. CD8+ T-cells provide broadly cross-reactive immunity and alleviate disease severity by recognizing conserved epitopes. Despite the IBV burden, only 18 IBV-specific T-cell epitopes restricted by 5 HLAs have been identified currently. A broader array of conserved IBV T-cell epitopes is needed to develop effective cross-reactive T-cell based IBV vaccines. Here we identify 9 highly conserved IBV CD8+ T-cell epitopes restricted to HLA-B*07:02, HLA-B*08:01 and HLA-B*35:01. Memory IBV-specific tetramer+CD8+ T-cells are present within blood and tissues. Frequencies of IBV-specific CD8+ T-cells decline with age, but maintain a central memory phenotype. HLA-B*07:02 and HLA-B*08:01-restricted NP30-38 epitope-specific T-cells have distinct T-cell receptor repertoires. We provide structural basis for the IBV HLA-B*07:02-restricted NS1196-206 (11-mer) and HLA-B*07:02-restricted NP30-38 epitope presentation. Our study increases the number of IBV CD8+ T-cell epitopes, and defines IBV-specific CD8+ T-cells at cellular and molecular levels, across tissues and age.",
author = "Tejas Menon and Illing, {Patricia T.} and Priyanka Chaurasia and McQuilten, {Hayley A.} and Chloe Shepherd and Rowntree, {Louise C.} and Jan Petersen and Littler, {Dene R.} and Grace Khuu and Ziyi Huang and Allen, {Lilith F.} and Steve Rockman and Jane Crowe and Flanagan, {Katie L.} and Wakim, {Linda M.} and Nguyen, {Thi H.O.} and Mifsud, {Nicole A.} and Jamie Rossjohn and Purcell, {Anthony W.} and {van de Sandt}, {Carolien E.} and Katherine Kedzierska",
note = "Funding Information: We thank the participating donors involved in the study as well as Bernadette McCudden for their medical support. We thank the Melbourne Cytometry Platform for the technical support and assistance. Computational resources for proteomics analysis were supported by the R@CMon/Monash Node of the NeCTAR Research Cloud, an initiative of the Australian Government\u2019s Super Science Scheme and the Education Investment Fund. The authors acknowledge the provision of instrumentation, training and technical support by the Monash Proteomics and Metabolomics Platform and thank Dr Marios Koutsakos for discussions. This work was supported by the Clifford Craig Foundation Project Grant to K.F. and K.K. (#186), the Research Grants Council of the Hong Kong Special Administrative Region, China (#T11-712/19-N) to K.K. and the NHMRC Leadership Investigator Grant to K.K. (#1173871) and Michelson Medical Research Foundation and Human Vaccines Project Michelson Prize for Human Immunology and Vaccine Research to P.T.I. P.T.I. was supported by Monash University Faculty of Medicine, Nursing and Health Sciences Senior Postdoctoral Fellowship (2020). C.S. is a recipient of the Australian Government Research Training Program Stipend. C.E.S. is supported by the ARC-DECRA Fellowship (#DE220100185) and the University of Melbourne Establishment Grant. T.H.O.N. is supported by the NHMRC Emerging Leadership Level 1 Investigator Grant (#1194036), J.R. is supported by an NHMRC Investigator Grant. A.W.P. is supported by a NHMRC Investigator grant (# 2016596). The project was support by a NIAID UO1 grant 1U01AI144616-01 \u201CDissection of Influenza Vaccination and Infection for Childhood Immunity\u201D (DIVINCI) and NIH contract CIVR-HRP (HHS-NIH-NIAID-BAA2018) to K.K. Funding Information: We thank the participating donors involved in the study as well as Bernadette McCudden for their medical support. We thank the Melbourne Cytometry Platform for the technical support and assistance. Computational resources for proteomics analysis were supported by the R@CMon/Monash Node of the NeCTAR Research Cloud, an initiative of the Australian Government\u2019s Super Science Scheme and the Education Investment Fund. The authors acknowledge the provision of instrumentation, training and technical support by the Monash Proteomics and Metabolomics Platform\u00A0and thank Dr Marios Koutsakos for discussions. This work was supported by the Clifford Craig Foundation Project Grant to K.F. and K.K. (#186), the Research Grants Council of the Hong Kong Special Administrative Region, China (#T11-712/19-N) to K.K. and the NHMRC Leadership Investigator Grant to K.K. (#1173871) and Michelson Medical Research Foundation and Human Vaccines Project Michelson Prize for Human Immunology and Vaccine Research to P.T.I. P.T.I. was supported by Monash University Faculty of Medicine, Nursing and Health Sciences Senior Postdoctoral Fellowship (2020). C.S. is a recipient of the Australian Government Research Training Program Stipend. C.E.S. is supported by the ARC-DECRA Fellowship (#DE220100185) and the University of Melbourne Establishment Grant. T.H.O.N. is supported by the NHMRC Emerging Leadership Level 1 Investigator Grant (#1194036), J.R. is supported by an NHMRC Investigator Grant. A.W.P. is supported by a NHMRC Investigator grant (# 2016596). The project was support by a NIAID UO1 grant 1U01AI144616-01 \u201CDissection of Influenza Vaccination and Infection for Childhood Immunity\u201D (DIVINCI) and NIH contract CIVR-HRP (HHS-NIH-NIAID-BAA2018) to K.K. Publisher Copyright: {\textcopyright} The Author(s) 2024.",
year = "2024",
month = apr,
day = "29",
doi = "10.1038/s41467-024-47576-y",
language = "English",
volume = "15",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
