Highly conserved cross-reactive CD4+ T-cell HA-epitopes of seasonal and the 2009 pandemic influenza viruses

Abstract

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.

Figure 1

Comparative epitope conservancy: (A) nH1N1 and sH1N1. (B) nH1N1 and H3N2, and (C) sH1N1 and H3N2. Note: sH1N1 (1985, 1989, 1990, 1992, 1993, 1994, 1997, 1998, 1999, and 2004) sequences and H3N2 (1979, 1981, 1982, 1984, 1987, 1989, 1991, and 1992) sequences are not available in National Center for Biotechnology Information Influenza database. Hence, they are not represented in these figures. Mutated epitopes within the same year are represented as year followed by a, b, c. Accession numbers are given in Table S7 of the supplementary information.

Figure 2

Predicted epitopes and functional related sites represented on the novel H1N1‐HA protein sequence.