Original Article: Highly conserved cross‐reactive CD4+ T‐cell HA‐epitopes of seasonal and the 2009 pandemic influenza viruses

Abstract

Please cite this paper as: Duvvuri et al. (2010) Highly conserved cross‐reactive CD4+ T‐cell HA‐epitopes of seasonal and the 2009 pandemic influenza viruses. Influenza and Other Respiratory Viruses 4(5), 249–258. 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.

Seroprevalence to Influenza A(H1N1) 2009 Virus—Where Are We?

“…That study found only two main sets of core motifs that would be beneficial to include in vaccines (14) to induce generic immune responses to influenza viruses. The HA T-cell epitopes of seasonal and 2009 pandemic strains have also shown a significant level of conservation (12).…”

Avian and Human Seasonal Influenza Hemagglutinin Proteins Elicit CD4 T Cell Responses That Are Comparable in Epitope Abundance and Diversity

“…Based on these studies, as well as our survey of human CD4 T cell reactivity to H7 HA (24), we speculated that the explanation behind the generally poor immunogenicity of avian HA relative to isolates from seasonal H1 and H3 HA proteins lies with the composition of the CD4 T cell memory compartment. Most humans have abundant CD4 T cell memory to epitopes contained within seasonal HA proteins (25,26), suggesting that it is this difference in the host that accounts for the overall ineffectiveness of avian vaccines. This contrasts with the speculation that avian HA proteins are inherently poorly immunogenic or have generalized deficits in T cell epitopes.…”

“…In order to do this, we utilized mouse models of vaccination, as virtually all human subjects have existing memory to seasonal H1N1 and H3N2 (25,26). We designed experiments to identify the number and abundance of MHC-II epitopes contained within H1, H3, H5, and H7 HA proteins that were recognized by CD4 T cells in an unbiased and comprehensive way.…”

A Human CD4+T Cell Epitope in the Influenza Hemagglutinin Is Cross-Reactive to Influenza A Virus Subtypes and to Influenza B Virus

“…The HA2 subunit, on the other hand, is more conserved among the different HA subtypes. Recently, an in silico study was done to evaluate the presence of cross-reactive T cell epitopes in the HA of seasonal influenza H1N1 and H3N2 viruses and the novel pandemic H1N1 virus (20). Duvvuri and colleagues found that CD4 ϩ T cell epitopes within different H1N1 strains were significantly conserved, while there were fewer conserved epitopes between the H3 and H1 subtypes (20).…”

“…Recently, an in silico study was done to evaluate the presence of cross-reactive T cell epitopes in the HA of seasonal influenza H1N1 and H3N2 viruses and the novel pandemic H1N1 virus (20). Duvvuri and colleagues found that CD4 ϩ T cell epitopes within different H1N1 strains were significantly conserved, while there were fewer conserved epitopes between the H3 and H1 subtypes (20). Although their findings suggest that cross-reactive T cells recognizing an epitope across all the different HA subtypes may be elusive, there are regions in the HA2 subunit, in particular the fusion peptide sequence, that are highly conserved in all the different HA subtypes (15).…”