Differential recognition of influenza A viruses by M158-66 epitopespecific CD8+ T cells is determined by extraepitopic amino acid residues

Journal of Virology

Volumn 90, Issue 2, 2016, Pages 1009-1022

  van de Sandt, Carolien E ^a   Kreijtz, Joost H C M ^a,c   Geelhoed Mieras, Martina M ^a   Nieuwkoop, Nella J ^a   Spronken, Monique I ^a   van de Vijver, David A M C ^a   Fouchier, Ron A M ^a   Osterhaus, Albert D M E ^a,b,d,e   Rimmelzwaan, Guus F ^a,b  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b ViroClinics Biosciences BV   (Netherlands)

^c Aduro BioTech Inc   (United States)

^d UNIVERSITY OF VETERINARY MEDICINE HANNOVER   (Germany)

^e Artemis One Health   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; EPITOPE; M1 PROTEIN, INFLUENZA A VIRUS; MATRIX PROTEIN;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANTIGEN PRESENTATION; ARTICLE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CONTROLLED STUDY; ENZYME LINKED IMMUNOSPOT ASSAY; HUMAN; HUMAN CELL; IMMUNE EVASION; INFLUENZA A VIRUS; INFLUENZA A VIRUS (H1N1); INFLUENZA A VIRUS (H2N2); INFLUENZA A VIRUS (H3N2); INFLUENZA A VIRUS (H5N1); NONHUMAN; PLASMID; PRIORITY JOURNAL; T LYMPHOCYTE ACTIVATION; VIRUS REPLICATION; CONSERVED SEQUENCE; GENETICS; IMMUNOLOGY;

CD8-POSITIVE T-LYMPHOCYTES; CONSERVED SEQUENCE; EPITOPES; HUMANS; IMMUNE EVASION; INFLUENZA A VIRUS; VIRAL MATRIX PROTEINS;

EID: 84954142443     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.02439-15     Document Type: Article

References (75)

1. WHO. 2015. Influenza (seasonal) fact sheet no. 211. http://www.who.int/mediacentre/factsheets/fs211/en/index.html. Accessed 27 June 2015.
2. Palese P, Shaw ML. 2007. Orthomyxoviridae: the viruses and their replication, p 1647-1689. In Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE (ed), Fields virology, 5th ed, vol 2. Lippincott Williams & Wilkins, Philadelphia, PA.
3. Tong S, Zhu X, Li Y, Shi M, Zhang J, Bourgeois M, Yang H, Chen X, Recuenco S, Gomez J, Chen LM, Johnson A, Tao Y, Dreyfus C, Yu W, McBride R, Carney PJ, Gilbert AT, Chang J, Guo Z, Davis CT, Paulson JC, Stevens J, Rupprecht CE, Holmes EC, Wilson IA, Donis RO. 2013. New world bats harbor diverse influenza A viruses. PLoS Pathog 9:e1003657. http://dx.doi.org/10.1371/journal.ppat.1003657.
4. Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y. 1992. Evolution and ecology of influenza A viruses. Microbiol Rev 56:152-179.
5. Schrauwen EJ, Fouchier RA. 2014. Host adaptation and transmission of influenza A viruses in mammals. Emerg Microbes Infect 3:e9. http://dx.doi.org/10.1038/emi.2014.9.
6. Smith GJ, Bahl J, Vijaykrishna D, Zhang J, Poon LL, Chen H, Webster RG, Peiris JS, Guan Y. 2009. Dating the emergence of pandemic influenza viruses. Proc Natl Acad Sci U S A 106:11709-11712. http://dx.doi.org/10.1073/pnas.0904991106.
7. Worobey M, Han GZ, Rambaut A. 2014. Genesis and pathogenesis of the 1918 pandemic H1N1 influenza A virus. Proc Natl Acad Sci U S A 111: 8107-8112. http://dx.doi.org/10.1073/pnas.1324197111.
8. Scholtissek C, Rohde W, Von Hoyningen V, Rott R. 1978. On the origin of the human influenza virus subtypes H2N2 and H3N2. Virology 87:13-20. http://dx.doi.org/10.1016/0042-6822(78)90153-8.
9. Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, Sessions WM, Xu X, Skepner E, Deyde V, Okomo-Adhiambo M, Gubareva L, Barnes J, Smith CB, Emery SL, Hillman MJ, Rivailler P, Smagala J, de Graaf M, Burke DF, Fouchier RA, Pappas C, Alpuche-Aranda CM, Lopez-Gatell H, Olivera H, Lopez I, Myers CA, Faix D, Blair PJ, Yu C, Keene KM, Dotson PD, Jr, Boxrud D, Sambol AR, Abid SH, St George K, Bannerman T, Moore AL, Stringer DJ, Blevins P, Demmler-Harrison GJ, Ginsberg M, Kriner P, Waterman S, Smole S, Guevara HF, Belongia EA, Clark PA, Beatrice ST, Donis R, Katz J, Finelli L, Bridges CB, Shaw M, Jernigan DB, Uyeki TM, Smith DJ, Klimov AI, Cox NJ. 2009. Antigenic and genetic characteristics of swineorigin 2009 A(H1N1) influenza viruses circulating in humans. Science 325:197-201. http://dx.doi.org/10.1126/science.1176225.
10. Wiley DC, Wilson IA, Skehel JJ. 1981. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 289:373-378. http://dx.doi.org/10.1038/289373a0.
11. Koel BF, Burke DF, Bestebroer TM, van der Vliet S, Zondag GC, Vervaet G, Skepner E, Lewis NS, Spronken MI, Russell CA, Eropkin MY, Hurt AC, Barr IG, de Jong JC, Rimmelzwaan GF, Osterhaus AD, Fouchier RA, Smith DJ. 2013. Substitutions near the receptor binding site determine major antigenic change during influenza virus evolution. Science 342:976-979. http://dx.doi.org/10.1126/science.1244730.
12. Smith DJ, Lapedes AS, de Jong JC, Bestebroer TM, Rimmelzwaan GF, Osterhaus AD, Fouchier RA. 2004. Mapping the antigenic and genetic evolution of influenza virus. Science 305:371-376. http://dx.doi.org/10.1126/science.1097211.
13. van de Sandt CE, Kreijtz JH, Rimmelzwaan GF. 2012. Evasion of influenza A viruses from innate and adaptive immune responses. Viruses 4:1438-1476. http://dx.doi.org/10.3390/v4091438.
14. Quinones-Parra S, Loh L, Brown LE, Kedzierska K, Valkenburg SA. 2014. Universal immunity to influenza must outwit immune evasion. Front Microbiol 5:285. http://dx.doi.org/10.3389/fmicb.2014.00285.
15. Neefjes J, Jongsma ML, Paul P, Bakke O. 2011. Towards a systems understanding ofMHCclass I andMHCclass II antigen presentation. Nat Rev 11:823-836. http://dx.doi.org/10.1038/nri3084.
16. Kreijtz JH, de Mutsert G, van Baalen CA, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. 2008. Cross-recognition of avian H5N1 influenza virus by human cytotoxic T-lymphocyte populations directed to human influenza A virus. J Virol 82:5161-5166. http://dx.doi.org/10.1128/JVI.02694-07.
17. van de Sandt CE, Kreijtz JH, de Mutsert G, Geelhoed-Mieras MM, Hillaire ML, Vogelzang-van Trierum SE, Osterhaus AD, Fouchier RA, Rimmelzwaan GF. 2014. Human cytotoxic T lymphocytes directed to seasonal influenza A viruses cross-react with the newly emerging H7N9 virus. J Virol 88:1684-1693. http://dx.doi.org/10.1128/JVI.02843-13.
18. Sridhar S, Begom S, Bermingham A, Hoschler K, Adamson W, Carman W, Bean T, Barclay W, Deeks JJ, Lalvani A. 2013. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med 19:1305-1312. http://dx.doi.org/10.1038/nm.3350.
19. Hayward AC, Wang L, Goonetilleke N, Fragaszy EB, Bermingham A, Copas A, Dukes O, Millett ER, Nazareth I, Nguyen-Van-Tam JS, Watson JM, Zambon M, Johnson AM, McMichael AJ, Flu Watch G. 2015. Natural T cell-mediated protection against seasonal and pandemic influenza. Results of the Flu Watch Cohort Study. Am J Respir Crit Care Med 191:1422-1431. http://dx.doi.org/10.1164/rccm.201411-1988OC.
20. Wang Z, Wan Y, Qiu C, Quinones-Parra S, Zhu Z, Loh L, Tian D, Ren Y, Hu Y, Zhang X, Thomas PG, Inouye M, Doherty PC, Kedzierska K, Xu J. 2015. Recovery from severe H7N9 disease is associated with diverse response mechanisms dominated by CD8(+) T cells. Nat Commun 6:6833. http://dx.doi.org/10.1038/ncomms7833.
21. Berkhoff EG, de Wit E, Geelhoed-Mieras MM, Boon AC, Symons J, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. 2005. Functional constraints of influenza A virus epitopes limit escape from cytotoxic T lymphocytes. J Virol 79:11239-11246. http://dx.doi.org/10.1128/JVI.79.17.11239-11246.2005.
22. Machkovech HM, Bedford T, Suchard MA, Bloom JD. 2015. Positive selection in CD8+ T-cell epitopes of influenza virus nucleoprotein revealed by a comparative analysis of human and swine viral lineages. J Virol 89:11275-11283. http://dx.doi.org/10.1128/JVI.01571-15.
23. Berkhoff EG, Geelhoed-Mieras MM, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. 2007. Assessment of the extent of variation in influenza A virus cytotoxic T-lymphocyte epitopes by using virusspecific CD8+T-cell clones. J Gen Virol 88:530-535. http://dx.doi.org/10.1099/vir.0.82120-0.
24. Boon AC, de Mutsert G, Graus YM, Fouchier RA, Sintnicolaas K, Osterhaus AD, Rimmelzwaan GF. 2002. Sequence variation in a newly identified HLA-B35-restricted epitope in the influenza A virus nucleoprotein associated with escape from cytotoxic T lymphocytes. J Virol 76:2567-2572. http://dx.doi.org/10.1128/jvi.76.5.2567-2572.2002.
25. Voeten JT, Bestebroer TM, Nieuwkoop NJ, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. 2000. Antigenic drift in the influenza A virus (H3N2) nucleoprotein and escape from recognition by cytotoxic T lymphocytes. J Virol 74:6800-6807. http://dx.doi.org/10.1128/JVI.74.15.6800-6807.2000.
26. Berkhoff EG, Boon AC, Nieuwkoop NJ, Fouchier RA, Sintnicolaas K, Osterhaus AD, Rimmelzwaan GF. 2004. A mutation in the HLA-B*2705-restricted NP383-391 epitope affects the human influenza A virus-specific cytotoxic T-lymphocyte response in vitro. J Virol 78:5216-5222. http://dx.doi.org/10.1128/JVI.78.10.5216-5222.2004.
27. Goulder PJ, Watkins DI. 2004. HIV and SIV CTL escape: implications for vaccine design. Nat Rev 4:630-640. http://dx.doi.org/10.1038/nrc1410.
28. Chang KM, Rehermann B, McHutchison JG, Pasquinelli C, Southwood S, Sette A, Chisari FV. 1997. Immunological significance of cytotoxic T lymphocyte epitope variants in patients chronically infected by the hepatitis C virus. J Clin Invest 100:2376-2385. http://dx.doi.org/10.1172/JCI119778.
29. Khanna R, Burrows SR, Moss DJ. 1995. Immune regulation in Epstein-Barr virus-associated diseases. Microbiol Rev 59:387-405.
30. Aebischer T, Moskophidis D, Rohrer UH, Zinkernagel RM, Hengartner H. 1991. In vitro selection of lymphocytic choriomeningitis virus escape mutants by cytotoxic T lymphocytes. Proc Natl Acad Sci U S A 88:11047-11051. http://dx.doi.org/10.1073/pnas.88.24.11047.
31. Morrison J, Elvin J, Latron F, Gotch F, Moots R, Strominger JL, McMichael A. 1992. Identification of the nonamer peptide from influenza A matrix protein and the role of pockets of HLA-A2 in its recognition by cytotoxic T lymphocytes. Eur J Immunol 22:903-907. http://dx.doi.org/10.1002/eji.1830220404.
32. Choo JA, Liu J, Toh X, Grotenbreg GM, Ren EC. 2014. The immunodominant influenza A virus M158-66 cytotoxic T lymphocyte epitope exhibits degenerate class I major histocompatibility complex restriction in humans. J Virol 88:10613-10623. http://dx.doi.org/10.1128/JVI.00855-14.
33. Furuse Y, Suzuki A, Kamigaki T, Oshitani H. 2009. Evolution of the M gene of the influenza A virus in different host species: large-scale sequence analysis. Virol J 6:67. http://dx.doi.org/10.1186/1743-422X-6-67.
34. Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. 2005. Characterization of the 1918 influenza virus polymerase genes. Nature 437:889-893. http://dx.doi.org/10.1038/nature04230.
35. Boon AC, de Mutsert G, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. 2006. The hypervariable immunodominant NP418-426 epitope from the influenza A virus nucleoprotein is recognized by cytotoxic T lymphocytes with high functional avidity. J Virol 80:6024-6032. http://dx.doi.org/10.1128/JVI.00009-06.
36. Sidney J, Grey HM, Kubo RT, Sette A. 1996. Practical, biochemical and evolutionary implications of the discovery of HLA class I supermotifs. Immunol Today 17:261-266. http://dx.doi.org/10.1016/0167-5699(96)80542-1.
37. Berkhoff EG, de Wit E, Geelhoed-Mieras MM, Boon AC, Symons J, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. 2006. Fitness costs limit escape from cytotoxic T lymphocytes by influenza A viruses. Vaccine 24: 6594-6596. http://dx.doi.org/10.1016/j.vaccine.2006.05.051.
38. Cao S, Liu X, Yu M, Li J, Jia X, Bi Y, Sun L, Gao GF, Liu W. 2012. A nuclear export signal in the matrix protein of Influenza A virus is required for efficient virus replication. J Virol 86:4883-4891. http://dx.doi.org/10.1128/JVI.06586-11.
39. Neisig A, Roelse J, Sijts AJ, Ossendorp F, Feltkamp MC, Kast WM, Melief CJ, Neefjes JJ. 1995. Major differences in transporter associated with antigen presentation (TAP)-dependent translocation of MHC class I-presentable peptides and the effect of flanking sequences. J Immunol 154:1273-1279.
40. Hofmann M, Nussbaum AK, Emmerich NP, Stoltze L, Schild H. 2001. Mechanisms of MHC class I-restricted antigen presentation. Expert Opin Ther Targets 5:379-393. http://dx.doi.org/10.1517/14728222.5.3.379.
41. Seifert U, Liermann H, Racanelli V, Halenius A, Wiese M, Wedemeyer H, Ruppert T, Rispeter K, Henklein P, Sijts A, Hengel H, Kloetzel PM, Rehermann B. 2004. Hepatitis C virus mutation affects proteasomal epitope processing. J Clin Invest 114:250-259. http://dx.doi.org/10.1172/JCI200420985.
42. Frisan T, Zhang QJ, Levitskaya J, Coram M, Kurilla MG, Masucci MG. 1996. Defective presentation of MHC class I-restricted cytotoxic T-cell epitopes in Burkitt's lymphoma cells. Int J Cancer 68:251-258. http://dx.doi.org/10.1002/(SICI)1097-0215(19961009)68:2<251;:AID-IJC19>3.0.CO;2-D.
43. Ito Y, Kondo E, Demachi-Okamura A, Akatsuka Y, Tsujimura K, Tanimoto M, Morishima Y, Takahashi T, Kuzushima K. 2006. Three immunoproteasome-associated subunits cooperatively generate a cytotoxic T-lymphocyte epitope of Epstein-Barr virus LMP2A by overcoming specific structures resistant to epitope liberation. J Virol 80:883-890. http://dx.doi.org/10.1128/JVI.80.2.883-890.2006.
44. Rimmelzwaan GF, Nieuwkoop N, Brandenburg A, Sutter G, Beyer WE, Maher D, Bates J, Osterhaus AD. 2000. A randomized, double blind study in young healthy adults comparing cell mediated and humoral immune responses induced by influenza ISCOM vaccines and conventional vaccines. Vaccine 19:1180-1187. http://dx.doi.org/10.1016/S0264-410X(00)00310-8.
45. Rimmelzwaan GF, Boon AC, Geelhoed-Mieras MM, Voeten JT, Fouchier RA, Osterhaus AD. 2004. Human airway epithelial cells present antigen to influenza virus-specific CD8+ CTL inefficiently after incubation with viral protein together with ISCOMATRIX. Vaccine 22:2769-2775. http://dx.doi.org/10.1016/j.vaccine.2004.01.052.
46. van Baalen CA, Kwa D, Verschuren EJ, Reedijk ML, Boon AC, de Mutsert G, Rimmelzwaan GF, Osterhaus AD, Gruters RA. 2005. Fluorescent antigen-transfected target cell cytotoxic T lymphocyte assay for ex vivo detection of antigen-specific cell-mediated cytotoxicity. J Infect Dis 192:1183-1190. http://dx.doi.org/10.1086/444546.
47. de Wit E, Spronken MI, Bestebroer TM, Rimmelzwaan GF, Osterhaus AD, Fouchier RA. 2004. Efficient generation and growth of influenza virus A/PR/8/34 from eightcDNAfragments. Virus research 103:155-161. http://dx.doi.org/10.1016/j.virusres.2004.02.028.
48. Hoffmann E, Neumann G, Kawaoka Y, Hobom G, Webster RG. 2000. A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci U S A 97:6108-6113. http://dx.doi.org/10.1073/pnas.100133697.
49. Rimmelzwaan GF, Baars M, Claas EC, Osterhaus AD. 1998. Comparison of RNA hybridization, hemagglutination assay, titration of infectious virus and immunofluorescence as methods for monitoring influenza virus replication in vitro. J Virol Methods 74:57-66. http://dx.doi.org/10.1016/S0166-0934(98)00071-8.
50. Voeten JT, Rimmelzwaan GF, Nieuwkoop NJ, Lovgren-Bengtsson K, Osterhaus AD. 2000. Introduction of the haemagglutinin transmembrane region in the influenza virus matrix protein facilitates its incorporation into ISCOM and activation of specific CD8(+) cytotoxic T lymphocytes. Vaccine 19:514-522.http://dx.doi.org/10.1016/S0264-410X(00)00179-1.
51. Benjamini Y, Hochberg Y. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 57:289-300.
52. Lamb RA, Lai CJ, Choppin PW. 1981. Sequences of mRNAs derived from genome RNA segment 7 of influenza virus: colinear and interrupted mRNAs code for overlapping proteins. Proc Natl Acad SciUSA 78:4170-4174. http://dx.doi.org/10.1073/pnas.78.7.4170.
53. Keskin DB, Reinhold BB, Zhang GL, Ivanov AR, Karger BL, Reinherz EL. 2015. Physical detection of influenza A epitopes identifies a stealth subset on human lung epithelium evading natural CD8 immunity. Proc Natl Acad Sci U S A 112:2151-2156. http://dx.doi.org/10.1073/pnas.1423482112.
54. van de Sandt CE, Rimmelzwaan GF. 2015. Immunodominant responses to the influenza virus M158-66 epitope: stealth or protection? Proc Natl Acad Sci U S A 112:E2417. http://dx.doi.org/10.1073/pnas.1503245112.
55. Boon AC, de Mutsert G, Graus YM, Fouchier RA, Sintnicolaas K, Osterhaus AD, Rimmelzwaan GF. 2002. The magnitude and specificity of influenza A virus-specific cytotoxic T-lymphocyte responses in humans is related to HLA-A and-B phenotype. J Virol 76:582-590. http://dx.doi.org/10.1128/JVI.76.2.582-590.2002.
56. Gueguen M, Biddison WE, Long EO. 1994. T cell recognition of an HLA-A2-restricted epitope derived from a cleaved signal sequence. J Exp Med 180:1989-1994. http://dx.doi.org/10.1084/jem.180.5.1989.
57. Saveanu L, Carroll O, Lindo V, Del Val M, Lopez D, Lepelletier Y, Greer F, Schomburg L, Fruci D, Niedermann G, van Endert PM. 2005. Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nat Immunol 6:689-697. http://dx.doi.org/10.1038/ni1208.
58. Cerundolo V, Benham A, Braud V, Mukherjee S, Gould K, Macino B, Neefjes J, Townsend A. 1997. The proteasome-specific inhibitor lactacystin blocks presentation of cytotoxic T lymphocyte epitopes in human and murine cells. Eur J Immunol 27:336-341. http://dx.doi.org/10.1002/eji.1830270148.
59. Luckey CJ, King GM, Marto JA, Venketeswaran S, Maier BF, Crotzer VL, Colella TA, Shabanowitz J, Hunt DF, Engelhard VH. 1998. Proteasomes can either generate or destroy MHC class I epitopes: evidence for nonproteasomal epitope generation in the cytosol. J Immunol 161:112-121.
60. Gileadi U, Moins-Teisserenc HT, Correa I, Booth BL, Jr, Dunbar PR, Sewell AK, Trowsdale J, Phillips RE, Cerundolo V. 1999. Generation of an immunodominant CTL epitope is affected by proteasome subunit composition and stability of the antigenic protein. J Immunol 163:6045-6052.
61. Vinitsky A, Anton LC, Snyder HL, Orlowski M, Bennink JR, Yewdell JW. 1997. The generation of MHC class I-associated peptides is only partially inhibited by proteasome inhibitors: involvement of nonproteasomal cytosolic proteases in antigen processing? J Immunol 159:554-564.
62. Geier E, Pfeifer G, Wilm M, Lucchiari-Hartz M, Baumeister W, Eichmann K, Niedermann G. 1999. A giant protease with potential to substitute for some functions of the proteasome. Science 283:978-981. http://dx.doi.org/10.1126/science.283.5404.978.
63. Seifert U, Maranon C, Shmueli A, Desoutter JF, Wesoloski L, Janek K, Henklein P, Diescher S, Andrieu M, de la Salle H, Weinschenk T, Schild H, Laderach D, Galy A, Haas G, Kloetzel PM, Reiss Y, Hosmalin A. 2003. An essential role for tripeptidyl peptidase in the generation of an MHC class I epitope. Nat Immunol 4:375-379. http://dx.doi.org/10.1038/ni905.
64. Del Val M, Schlicht HJ, Ruppert T, Reddehase MJ, Koszinowski UH. 1991. Efficient processing of an antigenic sequence for presentation by MHCclass I molecules depends on its neighboring residues in the protein. Cell 66:1145-1153. http://dx.doi.org/10.1016/0092-8674(91)90037-Y.
65. Eisenlohr LC, Yewdell JW, Bennink JR. 1992. Flanking sequences influence the presentation of an endogenously synthesized peptide to cytotoxic T lymphocytes. J Exp Med 175:481-487. http://dx.doi.org/10.1084/jem.175.2.481.
66. Yellen-Shaw AJ, Wherry EJ, Dubois GC, Eisenlohr LC. 1997. Point mutation flanking a CTL epitope ablates in vitro and in vivo recognition of a full-length viral protein. J Immunol 158:3227-3234.
67. Mo XY, Cascio P, Lemerise K, Goldberg AL, Rock K. 1999. Distinct proteolytic processes generate the C and N termini of MHC class I-binding peptides. J Immunol 163:5851-5859.
68. Gileadi U, Gallimore A, Van der Bruggen P, Cerundolo V. 1999. Effect of epitope flanking residues on the presentation of N-terminal cytotoxic T lymphocyte epitopes. Eur J immunology 29:2213-2222. http://dx.doi.org/10.1002/(SICI)1521-4141(199907)29:07<2213::AID-IMMU2213>3.0.CO;2-8.
69. Mathews JD, Chesson JM, McCaw JM, McVernon J. 2009. Understanding influenza transmission, immunity and pandemic threats. Influenza Other Respir Viruses 3:143-149. http://dx.doi.org/10.1111/j.1750-2659.2009.00089.x.
70. Dawood FS, Iuliano AD, Reed C, Meltzer MI, Shay DK, Cheng PY, Bandaranayake D, Breiman RF, Brooks WA, Buchy P, Feikin DR, Fowler KB, Gordon A, Hien NT, Horby P, Huang QS, Katz MA, Krishnan A, Lal R, Montgomery JM, Molbak K, Pebody R, Presanis AM, Razuri H, Steens A, Tinoco YO, Wallinga J, Yu H, Vong S, Bresee J, Widdowson MA. 2012. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis 12:687-695. http://dx.doi.org/10.1016/S1473-3099(12)70121-4.
71. Ikonen N, Strengell M, Kinnunen L, Osterlund P, Pirhonen J, Broman M, Davidkin I, Ziegler T, Julkunen I. 2010. High frequency of crossreacting antibodies against 2009 pandemic influenza A(H1N1) virus among the elderly in Finland. Euro Surveill 15:19478.
72. Hancock K, Veguilla V, Lu X, Zhong W, Butler EN, Sun H, Liu F, Dong L, DeVos JR, Gargiullo PM, Brammer TL, Cox NJ, Tumpey TM, Katz JM. 2009. Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med 361:1945-1952. http://dx.doi.org/10.1056/NEJMoa0906453.
73. He XS, Holmes TH, Zhang C, Mahmood K, Kemble GW, Lewis DB, Dekker CL, Greenberg HB, Arvin AM. 2006. Cellular immune responses in children and adults receiving inactivated or live attenuated influenza vaccines. J Virol 80:11756-11766. http://dx.doi.org/10.1128/JVI.01460-06.
74. Hoft DF, Babusis E, Worku S, Spencer CT, Lottenbach K, Truscott SM, Abate G, Sakala IG, Edwards KM, Creech CB, Gerber MA, Bernstein DI, Newman F, Graham I, Anderson EL, Belshe RB. 2011. Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children. J Infect Dis 204:845-853. http://dx.doi.org/10.1093/infdis/jir436.
75. Elliott T, Willis A, Cerundolo V, Townsend A. 1995. Processing of major histocompatibility class I-restricted antigens in the endoplasmic reticulum. J Exp Med 181:1481-1491. http://dx.doi.org/10.1084/jem.181.4.1481.