6pbh
Crystal Structure of HLA-A*68:01 in complex with NP145-156, a 12 mer influenza peptide
Structural highlights
Publication Abstract from PubMedAlthough 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 TCRalphabetas, while low-responders display A68/NP145(+)CD8(+) T cells with predominantly naive phenotypes and non-expanded TCRalphabetas. Single-cell index sorting and TCRalphabeta 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. Challenging immunodominance of influenza-specific CD8(+) T cell responses restricted by the risk-associated HLA-A*68:01 allomorph.,van de Sandt CE, Clemens EB, Grant EJ, Rowntree LC, Sant S, Halim H, Crowe J, Cheng AC, Kotsimbos TC, Richards M, Miller A, Tong SYC, Rossjohn J, Nguyen THO, Gras S, Chen W, Kedzierska K Nat Commun. 2019 Dec 6;10(1):5579. doi: 10.1038/s41467-019-13346-4. PMID:31811120[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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