1887

Abstract

Current influenza vaccines containing primarily hypervariable haemagglutinin and neuraminidase proteins must be prepared against frequent new antigenic variants. Therefore, there is an ongoing effort to develop influenza vaccines that also elicit strong and sustained cytotoxic responses against highly conserved determinants such as the matrix (M1) protein and nucleoprotein (NP). However, their antigenic presentation properties in humans are less defined. Accordingly, we analysed MHC class I and class II presentation of endogenously processed M1 and NP in human antigen presenting cells and observed expansion of both CD8- and CD4-specific effector T lymphocytes secreting gamma interferon and tumour necrosis factor. Further enhancement of basal MHC-II antigenic presentation did not improve CD4 or CD8 T-cell quality based on cytokine production upon challenge, suggesting that endogenous M1 and NP MHC-II presentation is sufficient. These new insights about T-lymphocyte expansion following endogenous M1 and NP MHC-I and -II presentation will be important to design complementary heterosubtypic vaccination strategies.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.029777-0
2011-05-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/92/5/1162.html?itemId=/content/journal/jgv/10.1099/vir.0.029777-0&mimeType=html&fmt=ahah

References

  1. Akondy R. S., Monson N. D., Miller J. D., Edupuganti S., Teuwen D., Wu H., Quyyumi F., Garg S., Altman J. D. et al. 2009; The yellow fever virus vaccine induces a broad and polyfunctional human memory CD8+ T cell response. J Immunol 183:7919–7930 [View Article][PubMed]
    [Google Scholar]
  2. Bachmann M. F., Wolint P., Schwarz K., Jäger P., Oxenius A. 2005; Functional properties and lineage relationship of CD8+ T cell subsets identified by expression of IL-7 receptor α and CD62L. J Immunol 175:4686–4696[PubMed] [CrossRef]
    [Google Scholar]
  3. Baumgarth N., Kelso A. 1996; In vivo blockade of gamma interferon affects the influenza virus-induced humoral and the local cellular immune response in lung tissue. J Virol 70:4411–4418[PubMed]
    [Google Scholar]
  4. Bednarek M. A., Sauma S. Y., Gammon M. C., Porter G., Tamhankar S., Williamson A. R., Zweerink H. J. 1991; The minimum peptide epitope from the influenza virus matrix protein. Extra and intracellular loading of HLA-A2. J Immunol 147:4047–4053[PubMed]
    [Google Scholar]
  5. Berkhoff E. G. M., de Wit E., Geelhoed-Mieras M. M., Boon A. C. M., Symons J., Fouchier R. A. M., Osterhaus A. D. M. E., Rimmelzwaan G. F. 2006; Fitness costs limit escape from cytotoxic T lymphocytes by influenza A viruses. Vaccine 24:6594–6596 [View Article][PubMed]
    [Google Scholar]
  6. Boettler T., Panther E., Bengsch B., Nazarova N., Spangenberg H. C., Blum H. E., Thimme R. 2006; Expression of the interleukin-7 receptor alpha chain (CD127) on virus-specific CD8+ T cells identifies functionally and phenotypically defined memory T cells during acute resolving hepatitis B virus infection. J Virol 80:3532–3540 [View Article][PubMed]
    [Google Scholar]
  7. Boon A. C. M., de Mutsert G., Graus Y. M. F., Fouchier R. A. M., Sintnicolaas K., Osterhaus A. D. M. E., Rimmelzwaan G. F. 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 [View Article][PubMed]
    [Google Scholar]
  8. Bui H.-H., Peters B., Assarsson E., Mbawuike I., Sette A. 2007; Ab and T cell epitopes of influenza A virus, knowledge and opportunities. Proc Natl Acad Sci U S A 104:246–251 [View Article][PubMed]
    [Google Scholar]
  9. Deng Y., Jing Y., Campbell A. E., Gravenstein S. 2004; Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly. J Immunol 172:3437–3446[PubMed] [CrossRef]
    [Google Scholar]
  10. De Rosa S. C., Lu F. X., Yu J., Perfetto S. P., Falloon J., Moser S., Evans T. G., Koup R., Miller C. J., Roederer M. 2004; Vaccination in humans generates broad T cell cytokine responses. J Immunol 173:5372–5380[PubMed] [CrossRef]
    [Google Scholar]
  11. Doucet, J.-D., Gauchat, D. & Lapointe, R. (2010). Identification of influenza T cell epitopes by a novel mRNA PCR-based epitope chasing technique. In Canadian Pandemic Preparedness Meeting: Outcomes, Impacts and Lessons Learned, abstract on. p. 45. Montreal, Quebec, Canada: Public Health Agency of Canada. http://www.ppsri-irscip.ca/print/handbook-010.pdf, accessed 21 February 2011.
  12. Epstein S. L., Tumpey T. M., Misplon J. A., Lo C. Y., Cooper L. A., Subbarao K., Renshaw M., Sambhara S., Katz J. M. 2002; DNA vaccine expressing conserved influenza virus proteins protective against H5N1 challenge infection in mice. Emerg Infect Dis 8:796–801[PubMed] [CrossRef]
    [Google Scholar]
  13. Furuya Y., Chan J., Regner M., Lobigs M., Koskinen A., Kok T., Manavis J., Li P., Müllbacher A., Alsharifi M. 2010; Cytotoxic T cells are the predominant players providing cross-protective immunity induced by gamma-irradiated influenza A viruses. J Virol 84:4212–4221 [View Article][PubMed]
    [Google Scholar]
  14. Gschoesser C., Almanzar G., Hainz U., Ortin J., Schonitzer D., Schild H., Saurwein-Teissl M., Grubeck-Loebenstein B. 2002; CD4+ and CD8+ mediated cellular immune response to recombinant influenza nucleoprotein. Vaccine 20:3731–3738 [View Article][PubMed]
    [Google Scholar]
  15. Guéguen M., Long E. O. 1996; Presentation of a cytosolic antigen by major histocompatibility complex class II molecules requires a long-lived form of the antigen. Proc Natl Acad Sci U S A 93:14692–14697 [View Article][PubMed]
    [Google Scholar]
  16. Heiny A. T., Miotto O., Srinivasan K. N., Khan A. M., Zhang G. L., Brusic V., Tan T. W., August J. T. 2007; Evolutionarily conserved protein sequences of influenza A viruses, avian and human, as vaccine targets. PLoS ONE 2:e1190 [View Article][PubMed]
    [Google Scholar]
  17. Hikono H., Kohlmeier J. E., Ely K. H., Scott I., Roberts A. D., Blackman M. A., Woodland D. L. 2006; T-cell memory and recall responses to respiratory virus infections. Immunol Rev 211:119–132 [View Article][PubMed]
    [Google Scholar]
  18. Jameson J., Cruz J., Terajima M., Ennis F. A. 1999; Human CD8+ and CD4+ T lymphocyte memory to influenza A viruses of swine and avian species. J Immunol 162:7578–7583[PubMed]
    [Google Scholar]
  19. Janssen E. M., Lemmens E. E., Wolfe T., Christen U., von Herrath M. G., Schoenberger S. P. 2003; CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes. Nature 421:852–856 [View Article][PubMed]
    [Google Scholar]
  20. Jaraquemada D., Marti M., Long E. O. 1990; An endogenous processing pathway in vaccinia virus-infected cells for presentation of cytoplasmic antigens to class II-restricted T cells. J Exp Med 172:947–954 [View Article][PubMed]
    [Google Scholar]
  21. Kim J. H., Jacob J. 2009; DNA vaccines against influenza viruses. Curr Top Microbiol Immunol 333:197–210 [View Article][PubMed]
    [Google Scholar]
  22. Kohlmeier J. E., Miller S. C., Smith J., Lu B., Gerard C., Cookenham T., Roberts A. D., Woodland D. L. 2008; The chemokine receptor CCR5 plays a key role in the early memory CD8+ T cell response to respiratory virus infections. Immunity 29:101–113 [View Article][PubMed]
    [Google Scholar]
  23. Kreijtz J. H., de Mutsert G., van Baalen C. A., Fouchier R. A., Osterhaus A. D., Rimmelzwaan G. F. 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 [View Article][PubMed]
    [Google Scholar]
  24. Lapointe R., Bellemare-Pelletier A., Housseau F., Thibodeau J., Hwu P. 2003; CD40-stimulated B lymphocytes pulsed with tumor antigens are effective antigen-presenting cells that can generate specific T cells. Cancer Res 63:2836–2843[PubMed]
    [Google Scholar]
  25. Lee L. Y., Ha L. A., Simmons C., de Jong M. D., Chau N. V., Schumacher R., Peng Y. C., McMichael A. J., Farrar J. J. et al. 2008; Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals. J Clin Invest 118:3478–3490[PubMed]
    [Google Scholar]
  26. Lepage S., Lapointe R. 2006; Melanosomal targeting sequences from gp100 are essential for MHC class II-restricted endogenous epitope presentation and mobilization to endosomal compartments. Cancer Res 66:2423–2432 [View Article][PubMed]
    [Google Scholar]
  27. Maecker H. T., Umetsu D. T., DeKruyff R. H., Levy S. 1998; Cytotoxic T cell responses to DNA vaccination: dependence on antigen presentation via class II MHC. J Immunol 161:6532–6536[PubMed]
    [Google Scholar]
  28. McMichael A. J., Gotch F. M., Noble G. R., Beare P. A. 1983; Cytotoxic T-cell immunity to influenza. N Engl J Med 309:13–17 [View Article][PubMed]
    [Google Scholar]
  29. Miller J. D., van der Most R. G., Akondy R. S., Glidewell J. T., Albott S., Masopust D., Murali-Krishna K., Mahar P. L., Edupuganti S., Lalor S. 2008; Human effector and memory CD8+ T cell responses to smallpox and yellow fever vaccines. Immunity 28:710–722 [View Article][PubMed]
    [Google Scholar]
  30. Moss R. B. 2009; Prospects for control of emerging infectious diseases with plasmid DNA vaccines. J Immune Based Ther Vaccines 7:3 http://www.jibtherapies.com/content/7/1/3 [View Article][PubMed]
    [Google Scholar]
  31. Mueller S. N., Langley W. A., Carnero E., García-Sastre A., Ahmed R. 2010; Immunization with live attenuated influenza viruses that express altered NS1 proteins results in potent and protective memory CD8+ T-cell responses. J Virol 84:1847–1855 [View Article][PubMed]
    [Google Scholar]
  32. Nakanishi Y., Lu B., Gerard C., Iwasaki A. 2009; CD8+ T lymphocyte mobilization to virus-infected tissue requires CD4+ T-cell help. Nature 462:510–513 [View Article][PubMed]
    [Google Scholar]
  33. Nuchtern J. G., Biddison W. E., Klausner R. D. 1990; Class II MHC molecules can use the endogenous pathway of antigen presentation. Nature 343:74–76 [View Article][PubMed]
    [Google Scholar]
  34. Pelletier S., Tanguay S., Lee S., Gunaratnam L., Arbour N., Lapointe R. 2009; TGF-alpha as a candidate tumor antigen for renal cell carcinomas. Cancer Immunol Immunother 58:1207–1218 [View Article][PubMed]
    [Google Scholar]
  35. Price G. E., Soboleski M. R., Lo C.-Y., Misplon J. A., Pappas C., Houser K. V., Tumpey T. M., Epstein S. L. 2009; Vaccination focusing immunity on conserved antigens protects mice and ferrets against virulent H1N1 and H5N1 influenza A viruses. Vaccine 27:6512–6521 [View Article][PubMed]
    [Google Scholar]
  36. Rush C., Mitchell T., Garside P. 2002; Efficient priming of CD4+ and CD8+ T cells by DNA vaccination depends on appropriate targeting of sufficient levels of immunologically relevant antigen to appropriate processing pathways. J Immunol 169:4951–4960[PubMed] [CrossRef]
    [Google Scholar]
  37. Schmid D., Pypaert M., Münz C. 2007; Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 26:79–92 [View Article][PubMed]
    [Google Scholar]
  38. Schultze J. L., Michalak S., Seamon M. J., Dranoff G., Jung K., Daley J., Delgado J. C., Gribben J. G., Nadler L. M. 1997; CD40-activated human B cells: an alternative source of highly efficient antigen presenting cells to generate autologous antigen-specific T cells for adoptive immunotherapy. J Clin Invest 100:2757–2765 [View Article][PubMed]
    [Google Scholar]
  39. Schweiger B., Zadow I., Heckler R. 2002; Antigenic drift and variability of influenza viruses. Med Microbiol Immunol (Berl) 191:133–138 [View Article][PubMed]
    [Google Scholar]
  40. Seder R. A., Darrah P. A., Roederer M. 2008; T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol 8:247–258 [View Article][PubMed]
    [Google Scholar]
  41. Skountzou I., Koutsonanos D. G., Kim J. H., Powers R., Satyabhama L., Masseoud F., Weldon W. C., Martin M. P., Mittler R. S. et al. 2010; Immunity to pre-1950 H1N1 influenza viruses confers cross-protection against the pandemic swine-origin 2009 A (H1N1) influenza virus. J Immunol 185:1642–1649 [View Article][PubMed]
    [Google Scholar]
  42. Swain S. L., Agrewala J. N., Brown D. M., Jelley-Gibbs D. M., Golech S., Huston G., Jones S. C., Kamperschroer C., Lee W.-H. et al. 2006; CD4+ T-cell memory: generation and multi-faceted roles for CD4+ T cells in protective immunity to influenza. Immunol Rev 211:8–22 [View Article][PubMed]
    [Google Scholar]
  43. Taylor P. M., Askonas B. A. 1986; Influenza nucleoprotein-specific cytotoxic T-cell clones are protective in vivo . Immunology 58:417–420[PubMed]
    [Google Scholar]
  44. Teijaro J. R., Verhoeven D., Page C. A., Turner D., Farber D. L. 2010; Memory CD4 T cells direct protective responses to influenza virus in the lungs through helper-independent mechanisms. J Virol 84:9217–9226 [View Article][PubMed]
    [Google Scholar]
  45. Thomas P. G., Keating R., Hulse-Post D. J., Doherty P. C. 2006; Cell-mediated protection in influenza infection. Emerg Infect Dis 12:48–54[PubMed] [CrossRef]
    [Google Scholar]
  46. Touvrey C., Derré L., Devevre E., Corthesy P., Romero P., Rufer N., Speiser D. E. 2009; Dominant human CD8 T cell clonotypes persist simultaneously as memory and effector cells in memory phase. J Immunol 182:6718–6726 [View Article][PubMed]
    [Google Scholar]
  47. Turcotte S., Forget M.-A., Beauseigle D., Nassif E., Lapointe R. 2007; Prostate-derived Ets transcription factor overexpression is associated with nodal metastasis and hormone receptor positivity in invasive breast cancer. Neoplasia 9:788–796 [View Article][PubMed]
    [Google Scholar]
  48. Van den Bosch G. A., Van Gulck E., Ponsaerts P., Nijs G., Lenjou M., Apers L., Kint I., Heyndrickx L., Vanham G. et al. 2006; Simultaneous activation of viral antigen-specific memory CD4+ and CD8+ T-cells using mRNA-electroporated CD40-activated autologous B-cells. J Immunother 29:512–523 [View Article][PubMed]
    [Google Scholar]
  49. Voo K. S., Fu T., Heslop H. E., Brenner M. K., Rooney C. M., Wang R.-F. 2002; Identification of HLA-DP3-restricted peptides from EBNA1 recognized by CD4+ T cells. Cancer Res 62:7195–7199[PubMed]
    [Google Scholar]
  50. WHO (2009 Pandemic (H1N1) 2009 http://www.who.int/csr/disease/swineflu/en/index.html accessed 10 March 2010
  51. Zhirnov O. P., Isaeva E. I., Konakova T. E., Thoidis G., Piskareva L. M., Akopova I. I., Kartashov A., Altstein A. D., Ilyinskii P. O., Shneider A. M. 2007; Protection against mouse and avian influenza A strains via vaccination with a combination of conserved proteins NP, M1 and NS1. Influenza Other Respir Viruses 1:71–79 [View Article][PubMed]
    [Google Scholar]
  52. Zhou Z., Jiang X., Liu D., Fan Z., Hu X., Yan J., Wang M., Gao G. F. 2009; Autophagy is involved in influenza A virus replication. Autophagy 5:321–328 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.029777-0
Loading
/content/journal/jgv/10.1099/vir.0.029777-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error