TY - JOUR
T1 - Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities
AU - Quinones-Parra, Sergio
AU - Grant, Emma
AU - Loh, Liyen
AU - Nguyen, Thi H. O.
AU - Campbell, Kristy-Anne
AU - Tong, Steven Y. C.
AU - Miller, Adrian
AU - Doherty, Peter C.
AU - Vijaykrishna, Dhanasekaran
AU - Rossjohn, Jamie
AU - Gras, Stephanie
AU - Kedzierska, Katherine
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
KW - CD8 T cells
KW - HLA types
UR - http://www.pnas.org/content/111/3/1049.full.pdf+html
U2 - 10.1073/pnas.1322229111
DO - 10.1073/pnas.1322229111
M3 - Article
VL - 111
SP - 1049
EP - 1054
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 3
ER -