7JYX

Crystal Structure of HLA A*2402 in complex with TYQWIIRNWET, an 11-mer epitope from Influenza

Summary for 7JYX

• Entry DOI: 10.2210/pdb7jyx/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, PB2 peptide from Influenza, TYQWIIRNWET, ... (4 entities in total)
• Functional Keywords: hla a*2402, influenza virus, tcr, t cell, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 90684.60

Authors

Gras, S.,Nguyen, A.T.,Szeto, C.,Rossjohn, J. (deposition date: 2020-09-01, release date: 2021-04-14, Last modification date: 2024-11-06)

Primary citation

Hensen, L.,Illing, P.T.,Bridie Clemens, E.,Nguyen, T.H.O.,Koutsakos, M.,van de Sandt, C.E.,Mifsud, N.A.,Nguyen, A.T.,Szeto, C.,Chua, B.Y.,Halim, H.,Rizzetto, S.,Luciani, F.,Loh, L.,Grant, E.J.,Saunders, P.M.,Brooks, A.G.,Rockman, S.,Kotsimbos, T.C.,Cheng, A.C.,Richards, M.,Westall, G.P.,Wakim, L.M.,Loudovaris, T.,Mannering, S.I.,Elliott, M.,Tangye, S.G.,Jackson, D.C.,Flanagan, K.L.,Rossjohn, J.,Gras, S.,Davies, J.,Miller, A.,Tong, S.Y.C.,Purcell, A.W.,Kedzierska, K.
CD8 + T cell landscape in Indigenous and non-Indigenous people restricted by influenza mortality-associated HLA-A*24:02 allomorph.
Nat Commun, 12:2931-2931, 2021

PubMed Abstract: Indigenous people worldwide are at high risk of developing severe influenza disease. HLA-A*24:02 allele, highly prevalent in Indigenous populations, is associated with influenza-induced mortality, although the basis for this association is unclear. Here, we define CD8 T-cell immune landscapes against influenza A (IAV) and B (IBV) viruses in HLA-A*24:02-expressing Indigenous and non-Indigenous individuals, human tissues, influenza-infected patients and HLA-A*24:02-transgenic mice. We identify immunodominant protective CD8 T-cell epitopes, one towards IAV and six towards IBV, with A24/PB2-specific CD8 T cells being cross-reactive between IAV and IBV. Memory CD8 T cells towards these specificities are present in blood (CD27CD45RA phenotype) and tissues (CD103CD69 phenotype) of healthy individuals, and effector CD27CD45RAPD-1CD38CD8 T cells in IAV/IBV patients. Our data show influenza-specific CD8 T-cell responses in Indigenous Australians, and advocate for T-cell-mediated vaccines that target and boost the breadth of IAV/IBV-specific CD8 T cells to protect high-risk HLA-A*24:02-expressing Indigenous and non-Indigenous populations from severe influenza disease.

PubMed: 34006841
DOI: 10.1038/s41467-021-23212-x

Experimental method

X-RAY DIFFRACTION (2.95 Å)