Cytotoxic T Lymphocytes Specific for Influenza Virus

  • A. McMichael
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 189)


Influenza virus has proved an excellent model for the study of the specificity of cytotoxic T lymphocytes (CTL) and of the processing of viral antigens. Fundamental information about these processes has been gained in both mice and humans. At the same time, a considerable amount has been learned about the role of CTL in influenza viral infections, particularly in mice. The virus has proved to be a malleable tool because it can be readily grown, the full nucleotide structure has been determined (in the 1970s; reviewed in Lamb 1983), there are multiple antigenic variants, many of which have been sequenced, the three-dimensional structures of haemagglutinin and neuraminidase are known (Varghese et al. 1983; Wiley et al. 1981) and, for human studies, it has the advantage that it has infected a very high percentage of the population. All of these features combine to make this a safe and invaluable model for the study of theoretical aspects of T cell function as well as investigating the practical issues of how T cells control virus infections. Studies with influenza virus answered long-standing questions about the interaction between viral antigens and class I molecules of the major histocompatibility complex (MHC). Along the way came information about mutant and variant MHC molecules and the demonstration that peptide epitopes presented by class I MHC molecules are recognised by CTL. More recently, the virus has been invaluable for the elucidation of the antigenprocessing pathways.


Influenza Virus Internal Virus Protein Influenza Nucleoprotein Cerundolo Versus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anderson K, Cresswell P, Gammon M, Hermes J, Williamson A, Zweerink H (1991) En- dogenously synthesized peptide with an endoplasmic reticulum signal sequence sensitizes antigen processing mutant cells to class l-restricted cell-mediated lysis. J Exp Med 174 (2): 489–492PubMedGoogle Scholar
  2. Askonas BA, McMichael AJ, Webster, RG (1982) The immune response to influenza virus and the problem of protection against infection. In: Beare AS (eds) Basic and applied influenza research CRC Press, Boca Raton, pp 157–188Google Scholar
  3. Bastin J, Rothbard J, Davey J, Jones I, Townsend, A (1987) Use of synthetic peptides of influenza nucleoprotein to define epitopes recognized by class I restricted cytotoxic T lymphocytes. J Exp Med 165:1508PubMedGoogle Scholar
  4. Bennink JR, Yewdell JW, Gerhard W (1982) A viral polymerase involved in recognition of influenza virus-infected cells by a cytotoxic T cell clone. Nature 296:75–76PubMedGoogle Scholar
  5. Bennink JR, Yewdell JW, Smith GL, Moller C, Moss B (1984) Recombinant vaccinia virus primes and stimulates influenza haemagglutinin-specific cytotoxic T cells. Nature 311 (5986): 578–579PubMedGoogle Scholar
  6. Bennink JR, Yewdell JW, Smith GL, Moss B (1986) Anti-influenza cytotoxic T lymphocytes recognise the three viral polymerases and a non-structural protein: reponsiveness to individual viral antigens is MHC controlled. J Virol 61:1098–1102Google Scholar
  7. Berzofsky JA (1991) Mechanisms of T cell recognition with application to vaccine design. Mol Immunol 28(3): 217–223PubMedGoogle Scholar
  8. Biddison WE, Ward FE, Shearer G M, Shaw S (1980) The self determinants recognised by human virus immune T cells can be distinguished from the serologically defined HLA antigens. J Immunol 124: 548–552PubMedGoogle Scholar
  9. Bjorkman P, Saper M, Samraoui B, Bennett W, Strominger J, Wiley D (1987a) Structure of human class I histocompatibility antigen, HLA-A2 Nature 329: 506–511Google Scholar
  10. Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC (1987b) The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature 329: 512–518PubMedGoogle Scholar
  11. Bodmer HC, Pemberton RM, Rothbard JB, Askonas BA (1988) Enhanced recognition of a modified peptide antigen by cytotoxic T lymphocytes specific for influenza nucleoprotein. Cell 52: 253–258PubMedGoogle Scholar
  12. Bowness PA, Moss PAH, Rowland-Jones SL, Bell Jl, McMichael AJ (1993) Conservation of T cell receptor usage by HLA B27-restricted influenza specific cytotoxic T lymphocytes suggests a general pattern for antigen-specific MHC class-l restricted responses. Eur J Immunol (in press)Google Scholar
  13. Braciale TJ, Braciale VL, Henkel TJ, Sambrook J, Gething M-J (1984) Cytotoxic T lymphocyte recognition of the influenza haemagglutinin gene product expressed by DNA mediated gene transfer. J Exp Med 159:341 -349PubMedGoogle Scholar
  14. Breuning MH, Lucas CJ, Breur BJ, Engelsma MY, DeLange GG, Dekker AJ, Biddison WE, Ivanyi P (1982) Subtypes of HLA B27 detected by cytotoxic T lymphocytes and their role in self recognition. Hum Immunol 5:259–268PubMedGoogle Scholar
  15. Buchmeier MJ, Welsh RM, Dutko FJ, Oldstone MBA (1980) The virology and immunology of lymphocytic choriomeningitis virus infection. Adv Immunol 30:275–331PubMedGoogle Scholar
  16. Cannon MJ, Openshaw PJM, Askonas B (1988) Cytotoxic cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus. J Exp Med 168:1163–1168PubMedGoogle Scholar
  17. Cerundolo V, Alexander J, Anderson K, Lamb C, Cresswell P, McMichael A, Gotch F, Townsend A (1990) Presentation of viral antigen controlled by a gene in the major histocompatibility complex. Nature 345 (6274): 449–452PubMedGoogle Scholar
  18. Cerundolo V, Tse AGD, Salter RD, Parham P, Townsend A (1991) CD8 independence and specificity of cytotoxic T lymphocytes restricted by HLA Aw68.1. Proc R Soc Lond [B] 244:169–177Google Scholar
  19. Colbert R, Rowland-Jones S, McMichael AJ, Frelinger J (1993) Proc Natl Acad Sci USA (in press)Google Scholar
  20. Cossins J, Gould KG, Smith M, Driscoll P, Brownlee, GG (1993) Precise prediction of a Kk-restricted cytotoxic T cell epitope in the NS1 protein of influenza virus using an MHC allele-specific motif. Virology 193 (1): 289–295PubMedGoogle Scholar
  21. Culmann B, Gomard E, Kieny M-P, Guy B, Dreyfus F, Saimot A-G, Sereni D, Sicar D, Levy J-P (1991) Six epitopes reacting with human cytotoxic CD8+ T cells in the central region of the HIV nef protein. J Immunol 146: 1560–1565PubMedGoogle Scholar
  22. Davis MM, Bjorkman PJ (1989) T-cell receptor genes and T-cell recognition. Nature 334: 395–402Google Scholar
  23. Deres K, Schild H, Weissmuller K-H, Jung G, Rammensee H-G (1989) In vivo priming of virus specific cytotoxic T lymphocytes with synthetic lipopeptide vaccine. Nature 342: 561 -564PubMedGoogle Scholar
  24. Deverson EV, Gow JR, Coadwell WJ, Monaco JJ, Butcher GW, Howard JC (1990) MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters. Nature 348:738–741PubMedGoogle Scholar
  25. Djaballah H, Rivett AJ (1992) Peptidylglutamyl-peptide hydrolase activity of the multicatalytic proteinase complex: evidence for a new high-affinity site, analysis of cooperative kinetics, and the effect of manganese ions. Biochemistry 31 (16): 4133–4141PubMedGoogle Scholar
  26. 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 -487PubMedGoogle Scholar
  27. Elliott T, Cerundolo V, Elvin J, Townsend A (1991) Peptide induced conformational change of a class I heavy chain. Nature 351:402PubMedGoogle Scholar
  28. Elliott T, Smith M, Driscoll P, McMichael A (1993) Peptide selection by class I molecules of the major histocompatibility complex. Current Biol (in press)Google Scholar
  29. Falk K, Rotzchke O, Deres K, Metzger J, Jung G, Rammensee H-G (1991a) Identification of naturally processed viral nonapeptides allows their quantification in infected cells and suggests an allele-specific T cell epitope forecast. J Exp Med 174:425–434PubMedGoogle Scholar
  30. Falk K, Rotzschke O, Stevanovic S, Jung G, Rammensee, H-G (1991b) Allele specific motifs revealed by sequencing of self peptides eluted from MHC molecules. Nature 351:290–296PubMedGoogle Scholar
  31. Foy HM, Cooney MK, Allan I (1976) Longitudinal studies of types A and B influenza among Seattle schoolchildren and their families, 1968–1974. J Infect Dis 134:362–369PubMedGoogle Scholar
  32. Fremont DH, Matsumura M, Stura EA, Peterson PA, Wilson IA (1992) Crystal structures of two viral peptides in complex with murine MHC class I H-2Kb. Science 257(5072): 919–927PubMedGoogle Scholar
  33. Gaczynska M, Rock KL, Goldberg AL (1993) γ-interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes. Nature 365: 264–267PubMedGoogle Scholar
  34. Gammon MC, Bednarek MA, Biddison WE, Bondy SS, Hermes JD, Mark GE, Williamson AR, Zweerink HJ (1992) Endogenous loading of HLA-A2 molecules with an analog of the influenza virus matrix protein-derived peptide and its inhibition by an exogenous peptide antagonist. J Immunol 148(1): 7–12PubMedGoogle Scholar
  35. Gao XM, Zheng B, Liew FY, Brett S, Tite J (1991) Priming of influenza virus-specific cytotoxic T lymphocytes vivo by short synthetic peptides. J Immunol 147(10): 3268–3273PubMedGoogle Scholar
  36. Gao X-M, Tite JP, Lipscombe M, Rowland-Jones S, Ferguson DJP, McMichael AJ (1992) Recombinant Salmonella typhimurium invading nonphagocytic cells are resistant to recognition by antigen specific cytotoxic T lymphocytes. Infect Immun 60:3780–3789PubMedGoogle Scholar
  37. Garrett TPJ, Saper MA, Bjorkman PJ, Strominger JL, Wiley DC (1989) Specificity pockets for the side chains of peptide antigens in HLA-Aw68. Nature 342:692PubMedGoogle Scholar
  38. Garten W, Stieneke A, Shaw E, Wikstrom P, Klenk H-D (1989) Inhibition of proteolytic activation of influenza virus hemagglutinin by specific peptidyl chloralkyl ketones. Virology 172:25–31PubMedGoogle Scholar
  39. Glynne R, Powis SH, Beck S, Kelly A, Kerr L-A, Trowsdale J (1991) A proteasome-related gene between the two ABC transporter loci in the class II region of the human MHC. Nature 353:357–359PubMedGoogle Scholar
  40. Gooding LR, O′Connell KA (1983) Recognition by cytotoxic T lymphocytes of cells expressing fragments of the SV40 tumour antigen. J Immunol 131:2580–2586PubMedGoogle Scholar
  41. Gotch FM, McMichael AJ, Smith GL, Moss B (1987a) Identification of the virus molecules recognised by influenza specific cytotoxic T lymphocytes. J Exp Med 165:408–416PubMedGoogle Scholar
  42. Gotch F, Rothbard J, Howland K, Townsend A, McMichael A (1987b) Cytotoxic T lymphocytes recognise a fragment of influenza virus matrix protein in association with HLA-A2. Nature 326:881–882PubMedGoogle Scholar
  43. Gotch FM, Hovell R, Delchambre M, Silvera P, McMichael AJ (1991) Cytotoxic T lymphocyte response simian immunodeficiency virus by cynomolgus macaque monkeys immunized with recombinant vaccinia virus. AIDS 5:317–320PubMedGoogle Scholar
  44. Gould KG, Scotney H, Brownlee GG (1991) Characterization of two distinct major histocompatibility complex class I Kk-restricted T-cell epitopes within the influenza A/PR/8/34 virus hemagglutinin. J Virol 65(10): 5401 -5409PubMedGoogle Scholar
  45. Gould KJ, Scotney H, Townsend ARM, Bastin J, Brownlee GG (1987) Mouse H-2k-restricted cytotoxic T cells recognize antigenic determinants in both the HA1 and HA2 subunits of the influenza A/PR/34 hemagglutinin. J Exp Med 166:693PubMedGoogle Scholar
  46. Guo H-C, Jardetzky TS, Garrett TP, Lane WS, Strominger JL, Wiley DC (1992) Different length peptides dind to HLA Aw68 similarly at their ends but bulge out in the middle. Nature 360: 364–366PubMedGoogle Scholar
  47. Hahn YS, Hahn CS, Braciale VL, Braciale TJ, Rice CM (1992) CD8+ T cell recognition of an endogenously processed epitope is regulated primarily by residues within the epitope. J Exp Med 176(5): 1335–1341PubMedGoogle Scholar
  48. Hoskins TW, Davies JR, Smith AJ, Miller CL, Allchin A (1979) Assessment of inactivated influenza A vaccine after three outbreaks of influenza A at Christ’s Hospital. Lancet i: 33–35Google Scholar
  49. Huet S, Nixon DF, Rothbard J, Townsend ARM, Ellis SA, McMichael AJ (1990) Structural homologies between two HLA B27 restricted peptides suggest residues important for interaction with HLA B27. Int Immunol 2:311–316PubMedGoogle Scholar
  50. Hunt DF, Henderson RA, Shabanowitz J, Sakaguchi K, Michel H, Sevilir N, Cox AL, Appella E, Engelhard VH (1992) Characterization of peptides bound to the class I MHC molecule HLA A2.1 by mass spectometry. Science 255:1261 -1263PubMedGoogle Scholar
  51. Jardetzky TS, Lane WS, Robinson RA, Madden DR, Wiley DC (1991) Identification of self peptides bound to purified HLA-B27. Nature 353:326–329PubMedGoogle Scholar
  52. Kelly A, Powis SH, Glynne R, Radley E, Beck S, Trowsdale J (1991) Second proteasome-related gene in the human MHC class II region. Nature 353:667–668PubMedGoogle Scholar
  53. Krangel MS, Taketani S, Biddison WE, Strong DM, Strominger JL (1982) Comparative structural analysis of H LA-A2 antigens distinguishable by cytoxic T lymphocytes: variants M7 and DR1. Biochemistry 21:6313–6321PubMedGoogle Scholar
  54. Kreth HW, Kress L, Kress HG, Ott HF, Eckert G (1982) Demonstration of primary cytotoxicTcells in venous blood and cerebrospinal fluid in children with mumps meningitis. J Immunol 128:2411–2415PubMedGoogle Scholar
  55. Lamb RA (1983) The influenza virus RNA segments and their encoded proteins. In: Palese P, Kingsbury D (eds) Genetics of influenza virus. Springer, Vienna New York, pp 21–69Google Scholar
  56. Latron F, Moots R, Rothbard J, Garrett T, Strominger JL, McMichael AJ (1991) Positioning of a peptide in the cleft of HLA A2 by complementing amino acid changes. Proc Natl Acad Sei USA 88:11325–11329Google Scholar
  57. Latron F, Pazmany L, Morrison JRM, Saper M, McMichael AJ, Strominger JL (1992) A critical role for conserved residues in the cleft of H LA-A2 in presentation of a nonapeptide to T cells. Science 257:964–967PubMedGoogle Scholar
  58. Levy F, Gabathuler R, Larsson R, Kvist S (1991) ATP is required for in vitro assembly of MHC class I antigens but not for transfer of paptides across the ER membrane. Cell (in press)Google Scholar
  59. Lin Y, Askonas BA (1981) Biological properties of an influenza A virus specific killer T cell clone. J Exp Med 154:225–234PubMedGoogle Scholar
  60. Ljunggren HG, Stam NJ, Ohlen C, Neefjes JJ, Hoglund P, Heemels MT, Bastin J, Schumacher TN, Townsend A, Karre K et al. (1990) Empty MHC class I molecules come out in the cold. Nature 346(6283): 476–480PubMedGoogle Scholar
  61. Lukacher AE, Braciale VL, Braciale TJ (1984) In vivo effector function of influenza virus specific cytotoxic T lymphocyte clones is highly specific. J Exp Med 160:814–826PubMedGoogle Scholar
  62. MacCallum FO (1971) Hypogammaglobulinaemia in the United Kingdom. 7. The role of humoral antibodies in protection against and recovery from bacterial and viral infections in hypogammaglobulinaemia. Med Res Engl 310:72–85Google Scholar
  63. Mackenzie CD, Taylor PM, Askonas BA (1989) Rapid recovery of lung histology correlates with clearance of influenza virus by specific CD8+ cytotoxic T cells. Immunology 67:375–381PubMedGoogle Scholar
  64. Madden DR, Gorgao JC, Strominger JL, Wiley DC (1992) The three dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for tight peptide binding to MHC. Cell 70:1035–1048PubMedGoogle Scholar
  65. Martinez CK, Monaco JJ (1991) Homology of the proteasome subunits to a major histocompatibility complex-linked LMP gene. Nature 353:664–667PubMedGoogle Scholar
  66. McMichael AJ (1978) HLA restriction of human cytotoxic T lymphocytes specific for influenza virus: poor recognition of virus associated with HLA A2. J Exp Med 148:1458PubMedGoogle Scholar
  67. McMichael AJ, Askonas BA (1978) Influenza virus specific cytotoxic T cells in man; induction and properties of the cytotoxic T cell. Eur J Immunol 8:705–710PubMedGoogle Scholar
  68. McMichael AJ, Ting A, Zweerink HJ, Askonas BA (1977) HLA restriction of cell mediated lysis of influenza virus infected human cells. Nature 270:524–526PubMedGoogle Scholar
  69. McMichael AJ, Gotch FM, Cullen P, Askonas BA, Webster RG (1981). The human cytotoxic T cell response to influenza A vaccination. Clin Exp Immunol 43:276–285PubMedGoogle Scholar
  70. McMichael AJ, Gotch FM, Dongworth DW, Clark A, Potter CW (1938a) Declining T cell immunity to influenza 1977–1982. Lancet ii: 762–764Google Scholar
  71. McMichael AJ, Gotch FM, Noble GR, Beare PAS (1983b) Cytotoxic T-cell immunity to influenza. N Engl J Med 309:13–17PubMedGoogle Scholar
  72. McMichael A, Gotch F, Rothbard J (1986) HLA B37 determines an influenza A virus nucleo- protein epitope recognized by cytotoxic T lymphocytes. J Exp Med 164(1397): 1397–1406PubMedGoogle Scholar
  73. Milligan GN, Morrison LA, Gorka J, Braciale VL, Braciale TJ (1990) The recognition of a viral antigenic moiety by class I MHC-restricted cytolytic T lymphocytes is limited by the availability of the endogenously processed antigen. J Immunol 145(10): 3188–3193PubMedGoogle Scholar
  74. Momburg F, Ortiz-Navarrete V, Neefjes J, Goulmy E, van de Wal Y, Spits H, Powis SJ, Butcher GW, Howard JC, Walden P, Hammerling GJ (1992) Proteasome subunits encoded by the major histocompatibility complex are not essential for antigen presentation. Nature 360: 174–177PubMedGoogle Scholar
  75. Monaco J, Cho S, Attaya M (1990) Transport protein genes in the murine MHC: possible implications for antigen processing. Science 250:1723–1726PubMedGoogle Scholar
  76. Morris AG, Lin Y-L, Askonas BA (1982) Immune interferon release when a cloned cytotoxic T cell meets its correct influenza-infected target cell. Nature 295:150–152PubMedGoogle Scholar
  77. Morrison J, Elvin J, Latron F, Gotch F, Moots R, Strominger JL, McMichael AJ (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 22:903–907PubMedGoogle Scholar
  78. Morrison LA, Lukacher AE, Braciale VL, Fan D, Braciale TJ (1986) Differences in antigen presentation to MHC class I- and class ll-restricted influenza virus-specific cytolytic T lymphocyte clones. J Exp Med 163: 903PubMedGoogle Scholar
  79. Moss PAH, Moots RJ, Rosenberg WMC, Rowland-Jones SJ, McMichael AJ, and Bell Jl (1991) Extensive conservation of alpha and beta chains of the human T cell antigen receptor recognizing HLA-A2 and influenza matrix peptide. Proc Natl Acad Sci USA 88:8987–8991PubMedGoogle Scholar
  80. Nathenson SG, Geliebter J, Pfaffenbach GM, Zeff RA (1986) Murine major histocompability complex class I mutants: molecular analysis and structure function implications. Annu Rev Immunol 4:471–521PubMedGoogle Scholar
  81. Nuchtern JG, Bonifacino JS, Biddison WE, Klausner RD (1989) Brefeldin A implicates egress from the endoplasmic reticulum in class I restricted antigen presentation. Nature 339:223–226PubMedGoogle Scholar
  82. Oehen S, Waldner H, Kundig TM, Hengartner H, Zinkernagel RM (1992) Antivirally protective cytotoxic T cell memory to lymphocytic choriomeningitis virus is governed by persisting antigen. J Exp Med 176(5): 1273–1281PubMedGoogle Scholar
  83. Ortiz-Navarette V, Seelig A, Gernold M, Frentzel S, Kloetzel PM, Hammerling GJ (1991) Subunit of the 20S proteasome (multicatalytic proteinase) encoded by the major histocompatibility complex. Nature 353:6662–6664Google Scholar
  84. Palese P, Young JK (1983) Molecular epidemiology of influenza virus. In: Palese P, Kingsbury D (eds) Genetics of influenza virus. Springer, Vienna New York, pp321 -326Google Scholar
  85. Parham P, Lomen CE, Lawlor DA, Ways JP, Holmes N, Coppin HL, Salter RD, Wan AM, Ennis PD (1988) Nature of polymorphism in HLA-A, -B and -C molecules. Proc Natl Acad Sci USA 85:4005–4009PubMedGoogle Scholar
  86. Parker KC, Bednarek MA, Hull LK, Utz U, Cunningham B, Zweerink HJ, Biddison WE, Coligan JE (1992) Sequence motifs important for peptide binding to the human MHC class I molecule, HLA-A2. J Immunol 149(11): 3580–3587PubMedGoogle Scholar
  87. Plata F, Autran B, Martins LP, Wain-Hobson S, Raphael M, Mayaud C, Denis M, Guillon JM, Debre P (1987) AIDS virus specific cytotoxic T lymphocytes in lung disorders. Nature 328:348–351PubMedGoogle Scholar
  88. Robertson L, Caley JP, Moore J (1958) Importance of staphylococcus aureus in pneumonia in the 1957 epidemic of influenza A. Lancet ii: 233–236Google Scholar
  89. Rotzschke O, Falk K (1991) Naturally-occurring peptide antigens derived from the MHC class-l-restricted processing pathway. Immunol Today 12(12): 447–455PubMedGoogle Scholar
  90. Sethi KK, Naher H, & Stroehmann I (1988) Phenotypic heterogeneity of cerebrospinal fluid- derived cytotoxic T cell clones. Nature 335:178–180PubMedGoogle Scholar
  91. Silver ML, Guo H-C, Stominger JL, Wiley DC (1992) Atomic structure of a human MHC molecule presenting an influenza virus peptide. Nature 360: 367–369PubMedGoogle Scholar
  92. Spies T, Bresnahan M, Bahram S, Arnold D, Blanck GEM, Pious D, DeMars R (1990) A gene in the major histocompatibility complex class II region controlling the class I antigen presentation pathway. Nature 348:744–747PubMedGoogle Scholar
  93. Spies T, Cerundolo V, Colonna M, Cresswell P, Townsend A, De Mars R (1992) Presentation of endogenous viral antigen dependent on putative peptide transporter heterodimer. Nature 355: 644–646PubMedGoogle Scholar
  94. Sutton J, Rowland-Jones S, Rosenberg W, Nixon D, Gotch F, Gao M, Murray N, Spoonas A, Driscoll P, Smith M, Willis A, McMichael AJ (1993) A sequence pattern for peptides presented to cytotoxic T lymphocytes by HLA B8 revealed by analysis of epitopes and eluted peptides. Eur J Immunol 23:447–453PubMedGoogle Scholar
  95. Takahashi H, Takeshita T, Morein B, Putney S, Germain RN, Berzofsky JA (1990) Induction of CD8+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs [see comments]. Nature 344(6269):873–875PubMedGoogle Scholar
  96. Tite JP, Hughes JC, O’Callaghan D, Dougan G, Russell SM, Gao XM, Liew FY (1990) Anti-viral immunity induced by recombinant nucleoprotein of influenza A virus. II. Protection from influenza infection and mechanism of protection. Immunology 71 (2): 202–207PubMedGoogle Scholar
  97. Townsend A, Bodmer H (1989) Antigen recognition by class l-restricted cytotoxic T lymphocytes. Annu Rev Immunol 7:601 -624PubMedGoogle Scholar
  98. Townsend ARM, Skehel JJ (1982) Influenza A specific cytotoxic T cell clones that do not recognise viral glycoproteins. Nature 300:655PubMedGoogle Scholar
  99. Townsend ARM, McMichael AJ, Carter NP, Huddlestone JA, Brownlee GG (1984) Cytotoxic T cell recognition of the influenza nucleoprotein and haemagglutinin expressed in transfected mouse L cells. Cell 39:13–25PubMedGoogle Scholar
  100. Townsend ARM, Gotch FM, Davey J (1985) Cytotoxic T cells recognize fragments of the influenza nucleoprotein. Cell 42:457–467PubMedGoogle Scholar
  101. Townsend ARM, Bastin J, Gould K, Brownlee GG (1986a) Cytotoxic T lymphocytes recognise influenza haemagglutinin that lacks a signal sequence. Nature 234:575Google Scholar
  102. Townsend ARM, Rothbard J, Gotch FM, Bahadur G, Wraith D, McMichael AJ, (1986b) The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44:959–968PubMedGoogle Scholar
  103. Townsend A, Ohlen C, Bastin J, Ljunggren HG, Foster L, Karre K (1989a) Association of class I major histocompatibility heavy and light chains induced by viral peptides. Nature 340(6233): 443–448PubMedGoogle Scholar
  104. Townsend A, Ohlen C, Foster L, Bastin J, Ljunggren HG, Karre K (1989b) A mutant cell in which association of class I heavy and light chains is induced by viral peptides. Cold Spring Harb Symp Quant Biol 1:299–308Google Scholar
  105. Townsend A, Elliott T, Cerundolo V, Foster L, Barber B, Tse A (1990) Assembly of MHC class I molecules analyzed in vitro. Cell 62 (2): 285–295PubMedGoogle Scholar
  106. Trowsdale J, Hanson I, Mockridge I, Beck S, Townsend ARM, Kelly A (1990) Sequences encoded in the class II region of the MHC related to the ABC superfamily of transporters. Nature 348:741 -744PubMedGoogle Scholar
  107. Ulmer J, Donnelly J J, Parker SE, Rhodes GH, Feigner PL, Dwarki VJ, Gromkowski SH, Deck RR, DeWitt CM, Friedman A, Hawe LA, Leander KR, Martinez D, Perry HC, Shiver JW, Montgomery DL, Liu MA (1993) Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259:1749–1749Google Scholar
  108. Varghese JN, Laver WG, Colman PM, (1983) Structure of the influenza glycoprotein antigen neuraminidase at 2.9A resolution. Nature 305:35–40Google Scholar
  109. Webster RG, Askonas BA (1980) Cross-protection and cross-reactive cytotoxic T-cells induced by influenza virus vaccines in mice. Eur J Immunol 10: 396–402PubMedGoogle Scholar
  110. Webster RG, Laver WG, Air GM, Schild GC (1982) Molecular mechanisms of variation in influenza viruses. Nature 296:115–121PubMedGoogle Scholar
  111. Wells MA, Ennis FA, Albrecht P (1981a) Recovery from a viral repsiratory tract infection. 1. Influenza pneumonia in normal and T deficient mice. J Immunol 126:1036–1041PubMedGoogle Scholar
  112. Wells MA, Ennis FA, Albrecht P (1981 b) Recovery from a viral respiratory infection. II. Passive transfer of immune spleen cells to mice with influenza pneumonia. J Immunol 126: 1042–1046PubMedGoogle Scholar
  113. 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 289:373–378PubMedGoogle Scholar
  114. Yap KL, Ada GL (1978a) Cytotoxic T cells in the lungs of mice infected with influenza A virus. Scand J Immunol 7: 73–80PubMedGoogle Scholar
  115. Yap KL, Ada GL (1978b) Transfer of specific cytotoxic T lymphocytes protects mice inoculated with influenza virus. Nature 273:238–240PubMedGoogle Scholar
  116. Yewdell JW, Bennink JR, Smith GL, Moss B (1985) Influenza A virus nucleoprotein is a major target for cross-reactive anti-influenza A virus specific cytotoxic T lymphocytes. Proc Natl Acad Sci USA 82:1785–1789PubMedGoogle Scholar
  117. Yewdell YW, Bennink JR (1989) Brefeldin A specifically inhibits presentation of protein antigens to cytotoxic T lymphocytes. Science 244:1072PubMedGoogle Scholar
  118. Zhang W, Young AC, Imarai M, Nathenson SG, Sacchettini JC (1992) Crystal structure of the major histocompatibility complex class I H-2Kb molecule containing a single viral peptide: implications for peptide binding and T-cell receptor recognition. Proc Natl Acad Sci USA 89 (17): 8403–8407PubMedGoogle Scholar
  119. Zinkernagel RM, Doherty PC (1979). MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T cell restriction-specificity, function and responsiveness. Adv Immunol 27:51PubMedGoogle Scholar
  120. Zweerink HJ, Gammon MC, Utz U, Sauma SY, Harrer T, Hawkins JC, Johnson RP, Sirotina A, Hermes JD, Walker BD, et al. (1993) Presentation of endogenous peptides to MHC class l-restricted cytotoxic T lymphocytes in transport deletion mutant T2 cells. J Immunol 1 50(5): 1763–1771Google Scholar
  121. Zweerink HT, Askonas BA, Mllican D, Courtneidge SA, Skehel JJ (1977) Cytotoxic T cells to type A influenza virus; viral haemagglutinin induces A-strain specificity while infected cells confer cross-reactive cytotoxicity. Eur J Immunol 7:630–635PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • A. McMichael
    • 1
  1. 1.Institute of Molecular MedicineJohn Radcliffe HospitalOxfordUK

Personalised recommendations