Projects per year
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.
Original language | English |
---|---|
Article number | 5579 |
Number of pages | 16 |
Journal | Nature Communications |
Volume | 10 |
Issue number | 1 |
DOIs | |
Publication status | Published - 6 Dec 2019 |
Keywords
- antigen presentation
- antimicrobial responses
- CD8-positive T cells
- influenza virus
Projects
- 2 Finished
-
ARC Centre of Excellence in Advanced Molecular Imaging
Whisstock, J., Abbey, B., Nugent, K., Quiney, H. M., Godfrey, D. I., Heath, W., Fairlie, D., Chapman, H., Peele, A., Davey, J. & Wittmann, A.
30/06/14 → 31/03/21
Project: Research