6PBH

Crystal Structure of HLA-A*68:01 in complex with NP145-156, a 12 mer influenza peptide

Summary for 6PBH

• Entry DOI: 10.2210/pdb6pbh/pdb
• Descriptor: HLA class I histocompatibility antigen, A-68 alpha chain, Beta-2-microglobulin, influenza A NP145-156 peptide, ... (7 entities in total)
• Functional Keywords: hla, influenza, tcr, t cell, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 45833.32

Authors

Gras, S. (deposition date: 2019-06-13, release date: 2019-12-11, Last modification date: 2024-10-16)

Primary citation

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.
Challenging immunodominance of influenza-specific CD8+T cell responses restricted by the risk-associated HLA-A*68:01 allomorph.
Nat Commun, 10:5579-5579, 2019

PubMed 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*68:01CD8 T cell response directed toward an extended influenza-derived nucleoprotein (NP) peptide and show that only ~35% individuals have immunodominant A68/NPCD8 T cell responses. Dissecting A68/NPCD8 T cells in low vs. medium/high responders reveals that high responding donors have A68/NPCD8 memory T cells with clonally expanded TCRαβs, while low-responders display A68/NPCD8 T cells with predominantly naïve phenotypes and non-expanded TCRαβs. Single-cell index sorting and TCRαβ analyses link expansion of A68/NPCD8 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.

PubMed: 31811120
DOI: 10.1038/s41467-019-13346-4

Experimental method

X-RAY DIFFRACTION (1.89 Å)