Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities

Quinones-Parra, Sergio, Grant, Emma, Loh, Liyen, Nguyen, Thi H.O., Campbell, Kristy-Anne, Tong, Steven Y.C., Miller, Adrian, Doherty, Peter C., Vijaykrishna, Dhanasekaran, Rossjohn, Jamie, Gras, Stephanie, and Kedzierska, Katherine (2014) Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities. Proceedings of the National Academy of Sciences of the United States of America, 111 (3). pp. 1049-1054.

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Abstract

The absence of preexisting neutralizing antibodies specific for the novel A (H7N9) influenza virus indicates a lack of prior human exposure. As influenza A virus–specific CD8+ T lymphocytes (CTLs) can be broadly cross-reactive, we tested whether immunogenic peptides derived from H7N9 might be recognized by memory CTLs established following infection with other influenza strains. Probing across multiple ethnicities, we identified 32 conserved epitopes derived from the nucleoprotein (NP) and matrix-1 (M1) proteins. These NP and M1 peptides are presented by HLAs prevalent in 16–57% of individuals. Remarkably, some HLA alleles (A*0201, A*0301, B*5701, B*1801, and B*0801) elicit robust CTL responses against any human influenza A virus, including H7N9, whereas ethnicities where HLA-A*0101, A*6801, B*1501, and A*2402 are prominent, show limited CTL response profiles. By this criterion, some groups, especially the Alaskan and Australian Indigenous peoples, would be particularly vulnerable to H7N9 infection. This dissection of CTL-mediated immunity to H7N9 thus suggests strategies for both vaccine delivery and development.

Item ID: 65203
Item Type: Article (Research - C1)
ISSN: 1091-6490
Keywords: CD8 T cells, HLA types
Copyright Information: Freely available online through the PNAS open access option. [Open access articles are published under a nonexclusive License to Publish and distributed under a Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) license]
Funders: National Health and Medical Research Council (NHMRC), University of Melbourne (UM), Consejo Nacional de Ciencia y Tecnología (CONACYT), Singapore Ministry of Education (SME), Agency for Science, Technology and Research, Singapore (A*STAR), Ministry of Health, Singapore
Projects and Grants: NHMRC AI1008854, NHMRC AI1042662, NHMRC AI567122, NHMRC Aboriginal and Torres Strait Islander Health Research Scholarship, SME Academic Research Fund Grant MOE2011-T2-2-049
Date Deposited: 29 Nov 2020 23:02
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111799 Public Health and Health Services not elsewhere classified @ 100%
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