HTML
-
All experimentally determined T cell epitopes were retrieved from IEDB database. A total of 223 MHC class Ⅰ-restricted epitopes with positive T cell response have been reported in influenza A viruses. We examined the presence of these CD8 T cell epitopes in seasonal influenza H1N1 and H3N2 virus subtypes (prior to emergence of pdmH1N1). As shown in Table 1, 151 epitopes were detected in seasonal H1N1 and H3N2 viruses. Of these, 81 were shared by both of them, 44 were unique to H1N1 and 26 unique to H3N2 virus. Most of the epitopes were located in viral internal NP, M1 and PB1 proteins, while few were in surface HA and NA proteins. Among the 151 seasonal influenza epitopes, 68.9% (104/151) were conserved in the novel H7N9 virus. A similar conservation level of these epitopes was also detected in pdmH1N1 (69.5%), H9N2 (68.2%) and H5N1 (71.5%) viruses. The conserved epitopes were mainly derived from viral NP, M1 and PB1 proteins (Table 2). As currently, a large number of humans have been exposed to pdmH1N1 prior to H7N9 outbreak, we further examined how many epitopes of seasonal H1N1, H3N2 plus pdmH1N1 viruses are conserved in the avian viruses. As shown in Table 3, 67.7% (113/167), 67.7% (113/167) and 73.1% (122/167) of these CD8 T cell epitopes were invariant in H7N9, H9N2 and H5N1 virus respectively.
Unique H1N1 Shared Unique H3N2 Total M1 4 28 3 35 M2 0 1 1 2 NP 22 13 17 52 PA 3 8 0 11 PB1 4 26 3 33 PB2 2 3 2 7 NS1 4 0 0 4 NS2 0 2 0 2 HA 3 0 0 3 NA 2 0 0 2 Total 44 81 26 151 Table 1. CD8 T cell epitopes in seasonal H1N1 & H3N2 viruses
Seasonal pitopes Conserved in H7N9 Conserved in pdmH1N1 Conserved in H9N2 Conserved in H5N1 M1 35 24 26 28 24 M2 2 0 0 0 0 NP 52 35 36 31 35 PA 11 9 8 6 9 PB1 33 27 28 29 30 PB2 7 5 4 5 5 NS1 4 1 0 1 1 NS2 2 2 1 2 1 HA 3 1 1 1 2 NA 2 0 1 0 1 Total 151 104 105 103 108 Table 2. Conservation of seasonal CD8 T cell epitopes in other viruses
Seasonal plus pdmH1N1 epitopes Conserved in H7N9 Conserved in H9N2 Conserved in H5N1 M1 37 24 28 25 M2 3 1 1 1 NP 60 40 36 42 PA 13 10 8 11 PB1 33 27 29 30 PB2 7 5 5 5 NS1 5 2 2 2 NS2 3 3 3 2 HA 3 1 1 2 NA 3 0 0 2 Total 167 113 113 122 Table 3. Conservation of seasonal plus pdmH1N1 CD8 epitopes in other viruses
-
We next examined the conservation of CD4 T cell epitopes. 687 MHC class Ⅱ-restricted epitopes with positive T cell response were obtained from the database, of which 199 and 189 epitopes were present in seasonal H1N1 and H3N2 virus respectively. Among them 71 were shared by both seasonal influenza viruses. Most of the epitopes were derived from HA, NP, M2 and NA proteins (Table 4). The conservation of these seasonal influenza viral epitopes in avian influenza viruses was further analyzed. As shown in Table 5, 23.3% (74/317) of these epitopes were conserved in H7N9 virus. Compared to H7N9 virus, a similar conservation level was shown in H9N2 (28.4%, 90/317) and H5N1 (25.6%, 81/317) virus, but a much higher level (31.9%, 101/317, p < 0.05) was conserved in pdmH1N1 virus. As with the CD8 T cell epitopes, the conserved CD4 T cell epitopes were mainly located in M1, NP and PB1 proteins. Few epitopes of surface HA and NA proteins were invariant in the avian influenza viruses. We also analyzed the conservation of CD4 T cell epitopes of seasonal H1N1, H3N2 plus pdmH1N1 viruses in avian influenza virus. As shown in Table 6, 22.1% (81/367), 27.2% (100/367) and 27.8% (102/367) of these epitopes remained invariant in H7N9, H9N2 and H5N1 virus respectively.
Unique H1N1 Shared Unique H3N2 Total M1 15 45 8 68 M2 1 0 0 1 NP 23 15 25 63 PA 1 2 1 4 PB1 5 8 2 15 PB2 1 0 2 3 NS1 6 1 3 10 NS2 2 0 1 3 HA 53 0 57 110 NA 21 0 19 40 Total 128 71 118 317 Table 4. CD4 T cell epitopes in seasonal H1N1 & H3N2 viruses
Seasonal epitopes Conserved in H7N9 Conserved in pdmH1N1 Conserved in H9N2 Conserved in H5N1 M1 68 32 40 40 35 M2 1 0 0 0 0 NP 63 24 25 24 21 PA 4 4 3 4 3 PB1 15 11 9 13 12 PB2 3 1 1 2 2 NS1 10 1 2 2 3 NS2 3 1 0 2 1 HA 110 0 18 0 0 NA 40 0 3 3 4 Total 317 74 101 90 81 Table 5. Conservation of seasonal CD4 T cell epitopes in other viruses
Seasonal plus pdmH1N1 epitopes Conserved in H7N9 Conserved in H9N2 Conserved in H5N1 M1 72 32 42 39 M2 1 0 0 0 NP 71 28 30 27 PA 4 4 4 3 PB1 17 13 14 14 PB2 4 2 3 3 NS1 10 1 2 3 NS2 3 1 2 1 HA 123 0 0 0 NA 62 0 3 12 Total 367 81 100 102 Table 6. Conservation of seasonal plus pdmH1N1 CD4 epitopes in other viruses