This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jameson, J.
Right arrow Articles by Ennis, F. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jameson, J.
Right arrow Articles by Ennis, F. A.

 Previous Article  |  Next Article 

Journal of Virology, November 1998, p. 8682-8689, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Human Cytotoxic T-Lymphocyte Repertoire to Influenza A Viruses

Julie Jameson, John Cruz, and Francis A. Ennis*

Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical Center, Worcester, Massachusetts 01655

Received 30 April 1998/Accepted 5 August 1998

The murine CD8+ cytotoxic-T-lymphocyte (CTL) repertoire appears to be quite limited in response to influenza A viruses. The CTL responses to influenza A virus in humans were examined to determine if the CTL repertoire is also very limited. Bulk cultures revealed that a number of virus proteins were recognized in CTL assays. CTL lines were isolated from three donors for detailed study and found to be specific for epitopes on numerous influenza A viral proteins. Eight distinct CD8+ CTL lines were isolated from donor 1. The proteins recognized by these cell lines included the nucleoprotein (NP), matrix protein (M1), nonstructural protein 1 (NS1), polymerases (PB1 and PB2), and hemagglutinin (HA). Two CD4+ cell lines, one specific for neuraminidase (NA) and the other specific for M1, were also characterized. These CTL results were confirmed by precursor frequency analysis of peptide-specific gamma interferon-producing cells detected by ELISPOT. The epitopes recognized by 6 of these 10 cell lines have not been previously described; 8 of the 10 cell lines were cross-reactive to subtype H1N1, H2N2, and H3N2 viruses, 1 cell line was cross-reactive to subtypes H1N1 and H2N2, and 1 cell line was subtype H1N1 specific. A broad CTL repertoire was detected in the two other donors, and cell lines specific for the NP, NA, HA, M1, NS1, and M2 viral proteins were isolated. These findings indicate that the human memory CTL response to influenza A virus is broadly directed to epitopes on a wide variety of proteins, unlike the limited response observed following infection of mice.

* Corresponding author. Mailing address: Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical Center, 55 Lake Ave. North, Worcester, MA 01655. Phone: (508) 856-4182. Fax: (508) 856-4890.

Journal of Virology, November 1998, p. 8682-8689, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Poon, L. L. M., Leung, Y. H. C., Nicholls, J. M., Perera, P.-Y., Lichy, J. H., Yamamoto, M., Waldmann, T. A., Peiris, J. S. M., Perera, L. P. (2009). Vaccinia Virus-Based Multivalent H5N1 Avian Influenza Vaccines Adjuvanted with IL-15 Confer Sterile Cross-Clade Protection in Mice. J. Immunol. 182: 3063-3071 [Abstract] [Full Text]  
  • Terajima, M., Cruz, J., Leporati, A. M., Orphin, L., Babon, J. A. B., Co, M. D. T., Pazoles, P., Jameson, J., Ennis, F. A. (2008). Influenza A Virus Matrix Protein 1-Specific Human CD8+ T-Cell Response Induced in Trivalent Inactivated Vaccine Recipients. J. Virol. 82: 9283-9287 [Abstract] [Full Text]  
  • Kreijtz, J. H. C. M., de Mutsert, G., van Baalen, C. A., Fouchier, R. A. M., Osterhaus, A. D. M. E., 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 [Abstract] [Full Text]  
  • Stoffels, R. J., Spencer, H. G. (2008). An Asymmetric Model of Heterozygote Advantage at Major Histocompatibility Complex Genes: Degenerate Pathogen Recognition and Intersection Advantage. Genetics 178: 1473-1489 [Abstract] [Full Text]  
  • Kotturi, M. F., Peters, B., Buendia-Laysa, F. Jr., Sidney, J., Oseroff, C., Botten, J., Grey, H., Buchmeier, M. J., Sette, A. (2007). The CD8+ T-Cell Response to Lymphocytic Choriomeningitis Virus Involves the L Antigen: Uncovering New Tricks for an Old Virus. J. Virol. 81: 4928-4940 [Abstract] [Full Text]  
  • Pasquetto, V., Bui, H.-H., Giannino, R., Mirza, F., Sidney, J., Oseroff, C., Tscharke, D. C., Irvine, K., Bennink, J. R., Peters, B., Southwood, S., Cerundolo, V., Grey, H., Yewdell, J. W., Sette, A. (2005). HLA-A*0201, HLA-A*1101, and HLA-B*0702 Transgenic Mice Recognize Numerous Poxvirus Determinants from a Wide Variety of Viral Gene Products. J. Immunol. 175: 5504-5515 [Abstract] [Full Text]  
  • Lindesmith, L., Moe, C., LePendu, J., Frelinger, J. A., Treanor, J., Baric, R. S. (2005). Cellular and Humoral Immunity following Snow Mountain Virus Challenge. J. Virol. 79: 2900-2909 [Abstract] [Full Text]  
  • Jegerlehner, A., Schmitz, N., Storni, T., Bachmann, M. F. (2004). Influenza A Vaccine Based on the Extracellular Domain of M2: Weak Protection Mediated via Antibody-Dependent NK Cell Activity. J. Immunol. 172: 5598-5605 [Abstract] [Full Text]  
  • Gervassi, A. L., Probst, P., Stamm, W. E., Marrazzo, J., Grabstein, K. H., Alderson, M. R. (2003). Functional Characterization of Class Ia- and Non-Class Ia-Restricted Chlamydia-Reactive CD8+ T Cell Responses in Humans. J. Immunol. 171: 4278-4286 [Abstract] [Full Text]  
  • Chen, H. D., Fraire, A. E., Joris, I., Welsh, R. M., Selin, L. K. (2003). Specific History of Heterologous Virus Infections Determines Anti-Viral Immunity and Immunopathology in the Lung. Am. J. Pathol. 163: 1341-1355 [Abstract] [Full Text]  
  • Danke, N. A., Kwok, W. W. (2003). HLA Class II-Restricted CD4+ T Cell Responses Directed Against Influenza Viral Antigens Postinfluenza Vaccination. J. Immunol. 171: 3163-3169 [Abstract] [Full Text]  
  • Whiteside, T. L., Zhao, Y., Tsukishiro, T., Elder, E. M., Gooding, W., Baar, J. (2003). Enzyme-linked Immunospot, Cytokine Flow Cytometry, and Tetramers in the Detection of T-Cell Responses to a Dendritic Cell-based Multipeptide Vaccine in Patients with Melanoma. Clin. Cancer Res. 9: 641-649 [Abstract] [Full Text]  
  • Van Epps, H. L., Terajima, M., Mustonen, J., Arstila, T. P., Corey, E. A., Vaheri, A., Ennis, F. A. (2002). Long-lived Memory T Lymphocyte Responses After Hantavirus Infection. JEM 196: 579-588 [Abstract] [Full Text]  
  • Mothe, B. R., Sidney, J., Dzuris, J. L., Liebl, M. E., Fuenger, S., Watkins, D. I., Sette, A. (2002). Characterization of the Peptide-Binding Specificity of Mamu-B*17 and Identification of Mamu-B*17-Restricted Epitopes Derived from Simian Immunodeficiency Virus Proteins. J. Immunol. 169: 210-219 [Abstract] [Full Text]  
  • Zivna, I., Green, S., Vaughn, D. W., Kalayanarooj, S., Stephens, H. A. F., Chandanayingyong, D., Nisalak, A., Ennis, F. A., Rothman, A. L. (2002). T Cell Responses to an HLA-B*07-Restricted Epitope on the Dengue NS3 Protein Correlate with Disease Severity. J. Immunol. 168: 5959-5965 [Abstract] [Full Text]  
  • Dercamp, C., Sanchez, V., Barrier, J., Trannoy, E., Guy, B. (2002). Depletion of Human NK and CD8 Cells prior to In Vitro H1N1 Flu Vaccine Stimulation Increases the Number of Gamma Interferon-Secreting Cells Compared to the Initial Undepleted Population in an ELISPOT Assay. CVI 9: 230-235 [Abstract] [Full Text]  
  • 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 [Abstract] [Full Text]  
  • Seo, S. H., Webster, R. G. (2001). Cross-Reactive, Cell-Mediated Immunity and Protection of Chickens from Lethal H5N1 Influenza Virus Infection in Hong Kong Poultry Markets. J. Virol. 75: 2516-2525 [Abstract] [Full Text]  
  • Basler, C. F., Reid, A. H., Dybing, J. K., Janczewski, T. A., Fanning, T. G., Zheng, H., Salvatore, M., Perdue, M. L., Swayne, D. E., Garcia-Sastre, A., Palese, P., Taubenberger, J. K. (2001). From the Cover: Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes. Proc. Natl. Acad. Sci. USA 98: 2746-2751 [Abstract] [Full Text]  
  • Voeten, J. T. M., Bestebroer, T. M., Nieuwkoop, N. J., Fouchier, R. A. M., Osterhaus, A. D. M. E., Rimmelzwaan, G. F. (2000). Antigenic Drift in the Influenza A Virus (H3N2) Nucleoprotein and Escape from Recognition by Cytotoxic T Lymphocytes. J. Virol. 74: 6800-6807 [Abstract] [Full Text]  
  • Epstein, S. L., Stack, A., Misplon, J. A., Lo, C.-Y., Mostowski, H., Bennink, J., Subbarao, K. (2000). Vaccination with DNA encoding internal proteins of influenza virus does not require CD8+ cytotoxic T lymphocytes: either CD4+ or CD8+ T cells can promote survival and recovery after challenge. Int Immunol 12: 91-101 [Abstract] [Full Text]  
  • Zivny, J., DeFronzo, M., Jarry, W., Jameson, J., Cruz, J., Ennis, F. A., Rothman, A. L. (1999). Partial Agonist Effect Influences the CTL Response to a Heterologous Dengue Virus Serotype. J. Immunol. 163: 2754-2760 [Abstract] [Full Text]  
  • Van Epps, H. L., Schmaljohn, C. S., Ennis, F. A. (1999). Human Memory Cytotoxic T-Lymphocyte (CTL) Responses to Hantaan Virus Infection: Identification of Virus-Specific and Cross-Reactive CD8+ CTL Epitopes on Nucleocapsid Protein. J. Virol. 73: 5301-5308 [Abstract] [Full Text]  
  • 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 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»