Details

Autor(en) / Beteiligte

• van de Sandt, C E
• Clemens, E B
• Grant, E J
• Rowntree, L C
• Sant, S
• Halim, H
• Crowe, J
• Cheng, A C
• Kotsimbos, T C
• Richards, M
• Miller, A
• Tong, S Y C
• Rossjohn, J
• Nguyen, T H O
• Gras, S
• Chen, W
• Kedzierska, K

Titel

Challenging immunodominance of influenza-specific CD8 + T cell responses restricted by the risk-associated HLA-A68:01 allomorph

Ist Teil von

• Nature communications, 2019-12, Vol.10 (1), p.5579-16, Article 5579

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2019

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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/NP CD8 T cell responses. Dissecting A68/NP CD8 T cells in low vs. medium/high responders reveals that high responding donors have A68/NP CD8 memory T cells with clonally expanded TCRαβs, while low-responders display A68/NP CD8 T cells with predominantly naïve phenotypes and non-expanded TCRαβs. Single-cell index sorting and TCRαβ analyses link expansion of A68/NP 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.