Discordant rearrangement of primary and anamnestic CD8+ T cell responses to influenza A viral epitopes upon exposure to bacterial superantigens: Implications for prophylactic vaccination, heterosubtypic immunity and superinfections

Autoři: Courtney E. Meilleur aff001;  Arash Memarnejadian aff001;  Adil N. Shivji aff001;  Jenna M. Benoit aff001;  Stephen W. Tuffs aff001;  Tina S. Mele aff002;  Bhagirath Singh aff001;  Jimmy D. Dikeakos aff001;  David J. Topham aff006;  Hong-Hua Mu aff007;  Jack R. Bennink aff008;  John K. McCormick aff001;  S. M. Mansour Haeryfar aff001
Působiště autorů: Department of Microbiology and Immunology, Western University, London, Ontario, Canada aff001;  Division of General Surgery, Department of Surgery, Western University, London, Ontario, Canada aff002;  Division of Critical Care Medicine, Department of Medicine, Western University, London, Ontario, Canada aff003;  Lawson Health Research Institute, London, Ontario, Canada aff004;  Centre for Human Immunology, Western University, London, Ontario, Canada aff005;  David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America aff006;  Division of Rheumatology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, United States of America aff007;  Viral Immunology Section, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America aff008;  Division of Clinical Immunology & Allergy, Department of Medicine, Western University, London, Ontario, Canada aff009
Vyšlo v časopise: Discordant rearrangement of primary and anamnestic CD8+ T cell responses to influenza A viral epitopes upon exposure to bacterial superantigens: Implications for prophylactic vaccination, heterosubtypic immunity and superinfections. PLoS Pathog 16(5): e32767. doi:10.1371/journal.ppat.1008393
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008393


Infection with (SAg)-producing bacteria may precede or follow infection with or vaccination against influenza A viruses (IAVs). However, how SAgs alter the breadth of IAV-specific CD8+ T cell (TCD8) responses is unknown. Moreover, whether recall responses mediating heterosubtypic immunity to IAVs are manipulated by SAgs remains unexplored. We employed wild-type (WT) and mutant bacterial SAgs, SAg-sufficient/deficient Staphylococcus aureus strains, and WT, mouse-adapted and reassortant IAV strains in multiple in vivo settings to address the above questions. Contrary to the popular view that SAgs delete or anergize T cells, systemic administration of staphylococcal enterotoxin B (SEB) or Mycoplasma arthritidis mitogen before intraperitoneal IAV immunization enlarged the clonal size of ‘select’ IAV-specific TCD8 and reshuffled the hierarchical pattern of primary TCD8 responses. This was mechanistically linked to the TCR Vβ makeup of the impacted clones rather than their immunodominance status. Importantly, SAg-expanded TCD8 retained their IFN-γ production and cognate cytolytic capacities. The enhancing effect of SEB on immunodominant TCD8 was also evident in primary responses to vaccination with heat-inactivated and live attenuated IAV strains administered intramuscularly and intranasally, respectively. Interestingly, in prime-boost immunization settings, the outcome of SEB administration depended strictly upon the time point at which this SAg was introduced. Accordingly, SEB injection before priming raised CD127highKLRG1low memory precursor frequencies and augmented the anamnestic responses of SEB-binding TCD8. By comparison, introducing SEB before boosting diminished recall responses to IAV-derived epitopes drastically and indiscriminately. This was accompanied by lower Ki67 and higher Fas, LAG-3 and PD-1 levels consistent with a pro-apoptotic and/or exhausted phenotype. Therefore, SAgs can have contrasting impacts on anti-IAV immunity depending on the naïve/memory status and the TCR composition of exposed TCD8. Finally, local administration of SEB or infection with SEB-producing S. aureus enhanced pulmonary TCD8 responses to IAV. Our findings have clear implications for superinfections and prophylactic vaccination.

Klíčová slova:

Cloning – Immune response – Influenza A virus – Major histocompatibility complex – Memory recall – Respiratory infections – T cells – Vaccination and immunization


1. Peters T, Hammon D, Jarrah R, Palavecino E, Blakeney E et al. Staphylococcal Toxic Shock Syndrome Complicating Influenza A Infection in a Young Child. ISRN Pulmonology. 2011;1–3.

2. Sion M, Hatzitolios A, Toulis E, Mikoudi K, Ziakas G et al. Toxic shock syndrome complicating influenza A infection: a two-case report with one case of bacteremia and endocarditis. Intensive Care Medicine. 2001;27(2):443. doi: 10.1007/s001340000803 11396292.

3. Florescu D, Kalil A. The complex link between influenza and severe sepsis. Virulence. 2013;5(1):137–142. doi: 10.4161/viru.27103 24253109.

4. Martin-Loeches I, Lemiale V, Geoghegan P, McMahon MA, Pickkers Pet al. Influenza and associated co-infections in critically ill immunosuppressed patients. Critical care (London, England). 2019;23(1):152. doi: 10.1186/s13054-019-2425-6 31046842.

5. Lindsay M. Hong Kong influenza: clinical, microbiologic, and pathologic features in 127 cases. JAMA: The Journal of the American Medical Association. 1970;214(10):1825–1832. doi: 10.1001/jama.214.10.1825 5537337.

6. Hers J, Masurel N, Mulder J. Bacteriology and Histopathology of the Respiratory Tract and Lungs in Fatal Asian Influenza. The Lancet. 1958;2(7057):1141–1143. doi: 10.1016/s0140-6736(58)92404-8 13612141.

7. Morens D, Taubenberger J, Fauci A. Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for Pandemic Influenza Preparedness. The Journal of Infectious Diseases. 2008;198(7):962–970. doi: 10.1086/591708 18710327.

8. Chertow D, Memoli M. Bacterial Coinfection in Influenza: a grand rounds review. JAMA. 2013;309(3):275. doi: 10.1001/jama.2012.194139 23321766.

9. Morris D, Cleary D, Clarke S. Secondary Bacterial Infections Associated with Influenza Pandemics. Frontiers in Microbiology. 2017;8:1041. doi: 10.3389/fmicb.2017.01041 28690590.

10. Herrmann T, Lees R, Robson MacDonald H, Baschieri S. In vivo responses of CD4+ and CD8+ cells to bacterial superantigens. European Journal of Immunology. 1992;22(7):1935–1938. doi: 10.1002/eji.1830220739 1623932.

11. Hayworth J, Mazzuca D, Vareki S, Welch I, McCormick J et al. CD1d-independent activation of mouse and human iNKT cells by bacterial superantigens. Immunology and Cell Biology. 2012;90(7):699–709. doi: 10.1038/icb.2011.90 22041925.

12. Shaler C, Choi J, Rudak P, Memarnejadian A, Szabo P et al. MAIT cells launch a rapid, robust and distinct hyperinflammatory response to bacterial superantigens and quickly acquire an anergic phenotype that impedes their cognate antimicrobial function: Defining a novel mechanism of superantigen-induced immunopathology and immunosuppression. PLOS Biology. 2017;15(6):e2001930. doi: 10.1371/journal.pbio.2001930 28632753.

13. Guo X, Thomas P. New fronts emerge in the influenza cytokine storm. Seminars in Immunopathology. 2017;39(5):541–550. 28555383.

14. Yewdell J, Haeryfar S. Understanding Presentation of Viral Antigens to CD8+ T Cells in Vivo: The Key to Rational Vaccine Design. Annual Review of Immunology. 2005;23:651–682. doi: 10.1146/annurev.immunol.23.021704.115702 15771583.

15. Brown L, Kelso A. Prospects for an influenza vaccine that induces cross-protective cytotoxic T lymphocytes. Immunology and Cell Biology. 2009;87(4):300–308. doi: 10.1038/icb.2009.16 19308073.

16. White J, Herman A, Pullen A, Kubo R, Kappler Jet al. The Vβ-specific superantigen staphylococcal enterotoxin B: Stimulation of mature T cells and clonal deletion in neonatal mice. Cell. 1989;56(1):27–35. doi: 10.1016/0092-8674(89)90980-x 2521300.

17. Miethke T, Wahl C, Gaus H, Heeg K, Wagner H. Exogenous superantigens acutely trigger distinct levels of peripheral T cell tolerance/immunosuppression: Dose-response relationship. European Journal of Immunology. 1994;24(8):1893–1902. doi: 10.1002/eji.1830240827 8056049.

18. Lussow A, MacDonald H. Differential effects of superantigen-induced “anergy” on priming and effector stages of a T cell-dependent antibody response. European Journal of Immunology. 1994;24(2):445–449. doi: 10.1002/eji.1830240227 8299694.

19. Meilleur C, Wardell C, Mele T, Dikeakos J, Bennink Jet al. Bacterial Superantigens Expand and Activate, Rather than Delete or Incapacitate, Preexisting Antigen-Specific Memory CD8+ T Cells. The Journal of Infectious Diseases. 2018;219(8):1307–1317. doi: 10.1093/infdis/jiy647 30418594.

20. Crowe S, Turner S, Miller S, Roberts A, Rappolo Ret al. Differential Antigen Presentation Regulates the Changing Patterns of CD8+ T Cell Immunodominance in Primary and Secondary Influenza Virus Infections. The Journal of Experimental Medicine. 2003;198(3):399–410. doi: 10.1084/jem.20022151 12885871.

21. Gileadi U, Moins-Teisserinc HT, Correa I, Booth BL Jr, Dunbar PRet al. Generation of an immunodominant CTL epitope is affected by proteasome subunit composition and stability of the antigenic protein. Journal of immunology. 1999;163(11):6045–6052. 10570292.

22. Probst H, Tschannen K, Gallimore A, Martinic M, Basler Met al. Immunodominance of an Antiviral Cytotoxic T Cell Response Is Shaped by the Kinetics of Viral Protein Expression. The Journal of Immunology. 2003;171(10):5415–5422. doi: 10.4049/jimmunol.171.10.5415 14607945.

23. Deng Y, Yewdell JW, Eisenlohr LC, Bennink JR. MHC affinity, peptide liberation, T cell repertoire, and immunodominance all contribute to the paucity of MHC class I-restricted peptides recognized by antiviral CTL. Journal of immunology. 1997;158(4)1507–1515. 9029084.

24. Chen W, Khilko S, Fecondo J, Margulies D, McCluskey J. Determinant selection of major histocompatibility complex class I-restricted antigenic peptides is explained by class I-peptide affinity and is strongly influenced by nondominant anchor residues. The Journal of Experimental Medicine. 1994;180(4):1471–1483. doi: 10.1084/jem.180.4.1471 7523572.

25. Kotturi M, Scott I, Wolfe T, Peters B, Sidney Jet al. Naive Precursor Frequencies and MHC Binding Rather Than the Degree of Epitope Diversity Shape CD8+ T Cell Immunodominance. The Journal of Immunology. 2008;181(3):2124–2133. doi: 10.4049/jimmunol.181.3.2124 18641351.

26. Haeryfar S, DiPaolo R, Tscharke D, Bennink J, Yewdell J. Regulatory T Cells Suppress CD8+ T Cell Responses Induced by Direct Priming and Cross-Priming and Moderate Immunodominance Disparities. The Journal of Immunology. 2005;174(6):3344–3351. doi: 10.4049/jimmunol.174.6.3344 15749866.

27. Rytelewski M, Meilleur C, Atef Yekta M, Szabo P, Garg Net al. Suppression of Immunodominant Antitumor and Antiviral CD8+ T Cell Responses by Indoleamine 2,3-Dioxygenase. PLoS ONE. 2014;9(2):e90439. doi: 10.1371/journal.pone.0090439 24587363.

28. Memarnejadian A, Meilleur C, Shaler C, Khazaie K, Bennink Jet al. PD-1 Blockade Promotes Epitope Spreading in Anticancer CD8+ T Cell Responses by Preventing Fratricidal Death of Subdominant Clones To Relieve Immunodomination. The Journal of Immunology. 2017;199(9):3348–3359. doi: 10.4049/jimmunol.1700643 28939757.

29. Haeryfar S, Hickman H, Irvine K, Tscharke D, Bennink Jet al. Terminal Deoxynucleotidyl Transferase Establishes and Broadens Antiviral CD8+ T Cell Immunodominance Hierarchies. The Journal of Immunology. 2008;181(1):649–659. doi: 10.4049/jimmunol.181.1.649 18566432.

30. Leon-Ponte M, Kasprzyski T, Mannik L, Haeryfar S. Altered Immunodominance Hierarchies of Influenza A Virus-Specific H-2b-Restricted CD8+T Cells in the Absence of Terminal Deoxynucleotidyl Transferase. Immunological Investigations. 2008;37:714–725. doi: 10.1080/08820130802349908 18821218.

31. Vareki S, Harding M, Waithman J, Zanker D, Shivji A et al. Differential Regulation of Simultaneous Antitumor and Alloreactive CD8+ T-Cell Responses in the Same Host by Rapamycin. American Journal of Transplantation. 2012;12(1):233–239. doi: 10.1111/j.1600-6143.2011.03811.x 22026814.

32. Irvine K, Bennink J. Factors influencing immunodominance hierarchies in TCD8+-mediated antiviral responses. Expert Review of Clinical Immunology. 2006;2(1):135–147. doi: 10.1586/1744666X.2.1.135 20477094.

33. Gilchuk P, Hill T, Wilson J, Joyce S. Discovering protective CD8 T cell epitopes—no single immunologic property predicts it!. Current Opinion in Immunology. 2015;34:43–51. doi: 10.1016/j.coi.2015.01.013 25660347.

34. Das S, Hensley S, Ince W, Brooke C, Subba Aet al. Defining Influenza A Virus Hemagglutinin Antigenic Drift by Sequential Monoclonal Antibody Selection. Cell Host & Microbe. 2013;13(3):314–323. doi: 10.1016/j.chom.2013.02.008 23498956.

35. Kilbourne ED. Future influenza vaccines and the use of genetic recombinants. Bulletin of the World Health Organization. 1969;41(3):643–645. 5309489.

36. Bennink J, Yewdell J, Gerhard W. A viral polymerase involved in recognition of influenza virus-infected cells by a cytotoxic T-cell clone. Nature. 1982;296(5852):75–76. doi: 10.1038/296075a0 6278312.

37. Xu S, Kasper K, Zeppa J, McCormick J. Superantigens Modulate Bacterial Density during Staphylococcus aureus Nasal Colonization. Toxins. 2015;7(5):1821–1836. doi: 10.3390/toxins7051821 26008236.

38. Atkin C, Wei S, Cole B. The Mycoplasma arthritidis superantigen MAM: purification and identification of an active peptide. Infection and Immunity. 1994;62(12):5367–5375. 7960116.

39. Chau T, McCully M, Brintnell W, An G, Kasper Ket al. Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome. Nature Medicine. 2009;15(6):641–648. doi: 10.1038/nm.1965 19465927.

40. Kappler J, Herman A, Clements J, Marrack P. Mutations defining functional regions of the superantigen staphylococcal enterotoxin B. The Journal of Experimental Medicine. 1992;175(2):387–396. doi: 10.1084/jem.175.2.387 1370682.

41. Leder L, Llera A, Lavoie P, Lebedeva M, Li Het al. A Mutational Analysis of the Binding of Staphylococcal Enterotoxins B and C3 to the T Cell Receptor β Chain and Major Histocompatibility Complex Class II. The Journal of Experimental Medicine. 1998;187(6):823–833. doi: 10.1084/jem.187.6.823 9500785.

42. Mu H, Pennock N, Humphreys J, Kirschning C, Cole B. Engagement of Toll-like receptors by mycoplasmal superantigen: downregulation of TLR2 by MAM/TLR4 interaction. Cellular Microbiology. 2005;7(6):789–797. doi: 10.1111/j.1462-5822.2005.00511.x 15888082.

43. Hayworth J, Kasper K, Leon-Ponte M, Herfst C, Yue Det al. Attenuation of massive cytokine response to the staphylococcal enterotoxin B superantigen by the innate immunomodulatory protein lactoferrin. Clinical & Experimental Immunology. 2009;157(1):60–70. doi: 10.1111/j.1365-2249.2009.03963.x 19659771.

44. Hosaka Y, Sasao F, Ohara R. Cell-mediated lysis of heat-inactivated influenza virus-coated murine targets. Vaccine. 1985;3:245–251. doi: 10.1016/0264-410x(85)90116-1 3877382.

45. Hufford M, Richardson G, Zhou H, Manicassamy B, García-Sastre A et al. Influenza-Infected Neutrophils within the Infected Lungs Act as Antigen Presenting Cells for Anti-Viral CD8+ T Cells. PLoS ONE. 2012;7(10):e46581. doi: 10.1371/journal.pone.0046581 23056353.

46. Szretter K, Balish A, Katz J. Influenza: Propagation, Quantification, and Storage. Current Protocols in Microbiology. 2006;3:15G.1.1–15G.1.22. doi: 10.1002/0471729256.mc15g01s3 18770580.

47. Killian M. Hemagglutination Assay for the Avian Influenza Virus. Methods in Molecular Biology. 2008;436:47–52. doi: 10.1007/978-1-59745-279-3_7 18370040.

48. Whitton J, Tishon A, Lewicki H, Gebhard J, Cook Tet al. Molecular analyses of a five-amino-acid cytotoxic T-lymphocyte (CTL) epitope: an immunodominant region which induces nonreciprocal CTL cross-reactivity. Journal of Virology. 1989;63(10):4303–4310. 2476570.

49. Choi J, Meilleur CE, Haeryfar SMM. Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses. Journal of visualized experiments: JoVE. 2019:147. doi: 10.3791/59531 31107454.

50. Benton K, Misplon J, Lo C, Brutkiewicz R, Prasad Set al. Heterosubtypic Immunity to Influenza A Virus in Mice Lacking IgA, All Ig, NKT Cells, or γδ T Cells. The Journal of Immunology. 2001;166(12):7437–7445. doi: 10.4049/jimmunol.166.12.7437 11390496.

51. Krummel M, Sullivan T, Allison J. Superantigen responses and co-stimulation: CD28 and CTLA-4 have opposing effects on T cell expansion in vitro and in vivo. International Immunology. 1996;8(4):519–523. doi: 10.1093/intimm/8.4.519 8671638.

52. Chen W, Bennink J, Morton P, Yewdell J. Mice Deficient in Perforin, CD4+ T Cells, or CD28-Mediated Signaling Maintain the Typical Immunodominance Hierarchies of CD8+ T-Cell Responses to Influenza Virus. Journal of Virology. 2002;76(20):10332–10337. doi: 10.1128/JVI.76.20.10332-10337.2002 12239309.

53. Robinson J, Pyle G, Kehoe M. Influence of major histocompatibility complex haplotype on the mitogenic response of T cells to staphylococcal enterotoxin B. Infection and Immunity. 1991;59(10):3667–3672. 1910013.

54. Reading P, Whitney P, Pickett D, Tate M, Brooks A. Influenza viruses differ in ability to infect macrophages and to induce a local inflammatory response following intraperitoneal injection of mice. Immunology and Cell Biology. 2010;88(6):641–650. doi: 10.1038/icb.2010.11 20142836.

55. Rötzschke O, Falk K, Deres K, Schild H, Norda Met al. Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature. 1990;348(6298):252–254. doi: 10.1038/348252a0 1700304.

56. Slütter B, Pewe L, Lauer P, Harty J. Cutting Edge: Rapid Boosting of Cross-Reactive Memory CD8 T Cells Broadens the Protective Capacity of the Flumist Vaccine. The Journal of Immunology. 2013;190(8):3854–3858. doi: 10.4049/jimmunol.1202790 23467935.

57. Adams J, Narayanan S, Liu B, Birnbaum M, Kruse Aet al. T Cell Receptor Signaling Is Limited by Docking Geometry to Peptide-Major Histocompatibility Complex. Immunity. 2011;35(5):681–693. doi: 10.1016/j.immuni.2011.09.013 22101157.

58. Li H, Llera A, Tsuchiya D, Leder L, Ysern Xet al. Three-Dimensional Structure of the Complex between a T Cell Receptor β Chain and the Superantigen Staphylococcal Enterotoxin B. Immunity. 1998;9(6):807–816. doi: 10.1016/s1074-7613(00)80646-9 9881971.

59. Jardetzky T, Brown J, Gorga J, Stern L, Urban Ret al. Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen. Nature. 1994;368(6473):711–718. doi: 10.1038/368711a0 8152483.

60. Fields B, Malchiodi E, Li H, Ysern X, Stauffacher Cet al. Crystal structure of a T-cell receptor β-chain complexed with a superantigen. Nature. 1996;384(6605):188–192. doi: 10.1038/384188a0 8906797.

61. Sundberg E, Deng L, Mariuzza R. TCR recognition of peptide/MHC class II complexes and superantigens. Seminars in Immunology. 2007;19(4):262–271. doi: 10.1016/j.smim.2007.04.006 17560120.

62. Cole B, Atkin C. The Mycoplasma arthritidis T-cell mitogen MAM: a model superantigen. Immunology Today. 1991;12(8):271–276. doi: 10.1016/0167-5699(91)90125-D 1910449.

63. Knudtson K, Manohar M, Joyner D, Ahmed E, Cole B. Expression of the superantigen Mycoplasma arthritidis mitogen in Escherichia coli and characterization of the recombinant protein. Infection and immunity. 1997;65(12):4965–4971. 9393783.

64. Li Z, Omoe K, Shinagawa K, Yagi J, Imanishi K. Interaction between superantigen and T-cell receptor Vβ element determines levels of superantigen-dependent cell-mediated cytotoxicity of CD8+T cells in induction and effector phases. Microbiology and Immunology. 2009;53(8):451–459. doi: 10.1111/j.1348-0421.2009.00136.x 19659929.

65. Pullen A, Marrack P, Kappler J. The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens. Nature. 1988;335(6193):796–801. doi: 10.1038/335796a0 3263572.

66. Woodland D, Lund F, Happ M, Blackman M, Palmer Eet al. Endogenous superantigen expression is controlled by mouse mammary tumor proviral loci. The Journal of Experimental Medicine. 1991;174(5):1255–1258. doi: 10.1084/jem.174.5.1255 1658187.

67. Araki K, Turner A, Shaffer V, Gangappa S, Keller Set al. mTOR regulates memory CD8 T-cell differentiation. Nature. 2009;460(7251):108–112. doi: 10.1038/nature08155 19543266.

68. Neumann B, Engelhardt B, Wagner H, Holzmann B. Induction of acute inflammatory lung injury by staphylococcal enterotoxin B. Journal of immunology. 1997;158(4):1862–1871. 9029127.

69. Herz U, Rückert R, Wollenhaupt K, Tschernig T, Neuhaus-Steinmetz U et al. Airway exposure to bacterial superantigen (SEB) induces lymphocyte-dependent airway inflammation associated with increased airway responsiveness–a model for non-allergic asthma. European Journal of Immunology. 1999;29(3):1021–1031. doi: 10.1002/(SICI)1521-4141(199903)29:03<1021::AID-IMMU1021>3.0.CO;2-3 10092107.

70. Rajagopalan G, Iijima K, Singh M, Kita H, Patel Ret al. Intranasal Exposure to Bacterial Superantigens Induces Airway Inflammation in HLA Class II Transgenic Mice. Infection and Immunity. 2006;74(2):1284–1296. doi: 10.1128/IAI.74.2.1284-1296.2006 16428778.

71. Borchardt S, Ritger K, Dworkin M. Categorization, Prioritization, and Surveillance of Potential Bioterrorism Agents. Infectious Disease Clinics of North America. 2006;20(2):213–225. doi: 10.1016/j.idc.2006.02.005 16762736.

72. Gaur A, Fathman CG, Steinman L, Brocke S. SEB induced anergy: modulation of immune response to T cell determinants of myoglobin and myelin basic protein. Journal of immunology. 1993;150(7):3062–3069. 7681087.

73. Sundstedt A, Höidén I, Hansson J, Hedlund G, Kalland Tet al. Superantigen-induced anergy in cytotoxic CD8+ T cells. Journal of immunology. 1995;154(12):6306–6313. 7759869.

74. Coppola MA, Blackman MA. Bacterial superantigens reactivate antigen-specific CD8+ memory T cells. International Immunology. 1997;9(9):1393–1403. doi: 10.1093/intimm/9.9.1393 9310843.

75. Wu C, Zanker D, Valkenburg S, Tan B, Kedzierska Ket al. Systematic identification of immunodominant CD8+ T-cell responses to influenza A virus in HLA-A2 individuals. Proceedings of the National Academy of Sciences. 2011;108(22):9178–9183. doi: 10.1073/pnas.1105624108 21562214.

76. Grant E, Wu C, Chan K, Eckle S, Bharadwaj Met al. Nucleoprotein of influenza A virus is a major target of immunodominant CD8+ T-cell responses. Immunology and Cell Biology. 2013;91(2):184–194. doi: 10.1038/icb.2012.78 23399741.

77. Grant E, Josephs T, Loh L, Clemens E, Sant Set al. Broad CD8+ T cell cross-recognition of distinct influenza A strains in humans. Nature Communications. 2018;9(1):5427. doi: 10.1038/s41467-018-07815-5 30575715.

78. Voeten J, Bestebroer T, Nieuwkoop N, Fouchier R, Osterhaus Aet al. Antigenic Drift in the Influenza A Virus (H3N2) Nucleoprotein and Escape from Recognition by Cytotoxic T Lymphocytes. Journal of Virology. 2000;74(15):6800–6807. doi: 10.1128/jvi.74.15.6800-6807.2000 10888619.

79. Boon A, de Mutsert G, Graus Y, Fouchier R, Sintnicolaas Ket al. Sequence Variation in a Newly Identified HLA-B35-Restricted Epitope in the Influenza A Virus Nucleoprotein Associated with Escape from Cytotoxic T Lymphocytes. Journal of Virology. 2002;76(5):2567–2572. doi: 10.1128/jvi.76.5.2567-2572.2002 11836437.

80. Huang C, Coppola M, Nguyen P, Carragher D, Rohl Cet al. Effect of Staphylococcus Enterotoxin B on the Concurrent CD8+ T Cell Response to Influenza Virus Infection. Cellular Immunology. 2000;204(1):1–10. doi: 10.1006/cimm.2000.1692 11006012.

81. Wu H, Kumar A, Miao H, Holden-Wiltse J, Mosmann Tet al. Modeling of Influenza-Specific CD8+ T Cells during the Primary Response Indicates that the Spleen Is a Major Source of Effectors. The Journal of Immunology. 2011;187(9):4474–4482. doi: 10.4049/jimmunol.1101443 21948988.

82. Altenburg A, Kreijtz J, de Vries R, Song F, Fux Ret al. Modified Vaccinia Virus Ankara (MVA) as Production Platform for Vaccines against Influenza and Other Viral Respiratory Diseases. Viruses. 2014;6(7):2735–2761. doi: 10.3390/v6072735 25036462.

83. de Vries R, Rimmelzwaan G. Viral vector-based influenza vaccines. Human Vaccines & Immunotherapeutics. 2016;12(11):2881–2901. doi: 10.1080/21645515.2016.1210729 27455345.

84. de Vries R, Altenburg A, Nieuwkoop N, de Bruin E, van Trierum S et al. Induction of Cross-Clade Antibody and T-Cell Responses by a Modified Vaccinia Virus Ankara–Based Influenza A(H5N1) Vaccine in a Randomized Phase 1/2a Clinical Trial. The Journal of Infectious Diseases. 2018;218(4):614–623. doi: 10.1093/infdis/jiy214 29912453.

85. Tscharke D, Woo W, Sakala I, Sidney J, Sette Aet al. Poxvirus CD8+ T-Cell Determinants and Cross-Reactivity in BALB/c Mice. Journal of Virology. 2006;80(13):6318–6323. doi: 10.1128/JVI.00427-06 16775319.

86. Hu Z, Molloy M, Usherwood E. CD4+ T-cell dependence of primary CD8+ T-cell response against vaccinia virus depends upon route of infection and viral dose. Cellular & Molecular Immunology. 2016;13(1):82–93. doi: 10.1038/cmi.2014.128 25544501.

Článek vyšel v časopise

PLOS Pathogens

2020 Číslo 5

Nejčtenější v tomto čísle

Zvyšte si kvalifikaci online z pohodlí domova

Antiseptika a prevence ve stomatologii
nový kurz
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Diagnostika a léčba deprese pro ambulantní praxi
Autoři: MUDr. Jan Hubeňák, Ph.D

Snímatelné zubní náhrady a fixační krémy
Autoři: doc. MUDr. Hana Hubálková, Ph.D.

Nová éra v léčbě migrény
Autoři: MUDr. Eva Medová, MUDr. Tomáš Nežádal, Ph.D.

Význam nutraceutik u kardiovaskulárních onemocnění

Všechny kurzy
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se