Highly conserved cross-reactive CD4+ T-cell HA-epitopes of seasonal and the 2009 pandemic influenza viruses.
BACKGROUND
The relatively mild nature of the 2009 influenza pandemic (nH1N1) highlights the overriding importance of pre-existing immune memory. The absence of cross-reactive antibodies to nH1N1 in most individuals suggests that such attenuation may be attributed to pre-existing cellular immune responses to epitopes shared between nH1N1 virus and previously circulating strains of inter-pandemic influenza A viruses.


RESULTS
We sought to identify potential CD4+ T cell epitopes and predict the level of cross-reactivity of responding T cells. By performing large-scale major histocompatibility complex II analyses on Hemagglutinin (HA) proteins, we investigated the degree of T-cell cross-reactivity between seasonal influenza A (sH1N1, H3N2) from 1968 to 2009 and nH1N1 strains. Each epitope was examined against all the protein sequences that correspond to sH1N1, H3N2, and nH1N1. T-cell cross-reactivity was estimated to be 52%, and maximum conservancy was found between sH1N1 and nH1N1 with a significant correlation (P < 0.05).


CONCLUSIONS
Given the importance of cellular responses in kinetics of influenza infection in humans, our findings underscore the role of T-cell assays for understanding the inter-pandemic variability in severity and for planning treatment methods for emerging influenza viruses.
Duvvuri
Venkata R S K
VR
MITACS Centre for Disease Modeling, York Institute of Health Research, Toronto, Ontario, Canada.
Moghadas
Seyed M
SM
Guo
Hongbin
H
Duvvuri
Bhargavi
B
Heffernan
Jane M
JM
Fisman
David N
DN
Wu
Gillian E
GE
Wu
Jianhong
J
D017124:Conserved Sequence; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006389:Hemagglutinins, Viral / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; C458881:hemagglutinin fusogenic peptide, influenza virus