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

C. E. Sandt, E. B. Clemens, E. J. Grant, L. C. Rowntree, S. Sant, H. Halim, J. Crowe, A. C. Cheng, T. C. Kotsimbos, M. Richards, A. Miller, S. Y. C. Tong, J. Rossjohn, T. H. O. Nguyen, S. Gras, W. Chen and K. Kedzierska ()
Additional contact information
C. E. Sandt: University of Melbourne at The Peter Doherty Institute
E. B. Clemens: University of Melbourne at The Peter Doherty Institute
E. J. Grant: University of Melbourne at The Peter Doherty Institute
L. C. Rowntree: University of Melbourne at The Peter Doherty Institute
S. Sant: University of Melbourne at The Peter Doherty Institute
H. Halim: Monash University
J. Crowe: Deepdene Surgery
A. C. Cheng: Monash University
T. C. Kotsimbos: Immunology and Respiratory Medicine, The Alfred Hospital
M. Richards: Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity
A. Miller: Griffith University
S. Y. C. Tong: Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity
J. Rossjohn: Monash University
T. H. O. Nguyen: University of Melbourne at The Peter Doherty Institute
S. Gras: Monash University
W. Chen: La Trobe University
K. Kedzierska: University of Melbourne at The Peter Doherty Institute

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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 expanded TCRαβs, while low-responders display A68/NP145+CD8+ T cells with predominantly naïve phenotypes and non-expanded TCRαβs. Single-cell index sorting and TCRαβ analyses link expansion of A68/NP145+CD8+ T cells to their memory potential. Our study demonstrates the immunodominance potential of influenza-specific CD8+ T cells presented by a risk HLA-A*68:01 molecule and advocates for priming CD8+ T cell compartments in HLA-A*68:01-expressing individuals for establishment of pre-existing protective memory T cell pools.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-13346-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13346-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-13346-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().