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Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105
Screening with the flow cytometric IFN-
assay has led to the
identification of a new immunogenic peptide (SSYRRVPGI) from the
influenza PB1 polymerase (PB1703–711) and a mimotope
(ISPLMVAYM) from the PB2 polymerase (PB2198–206).
CD8+ T cells specific for KbPB1703
make both IFN- and TNF-
following stimulation with both peptides.
The CD8+ KbPB1703+
population kills PB2198-pulsed targets, but cell lines
stimulated with PB2198 neither bind the
KbPB1703 tetramer nor become CTL. This
CD8+KbPB1703+
population is prominent in the primary response to an H3N2 virus,
although it is much less obvious following secondary challenge of
H1N1-primed mice. Even so, we can now account for >40% of the
CD8+ T cells in a primary influenza pneumonia and >85% of
those present after H3N2 
H1N1 challenge. Profiles of IFN- and
TNF- staining following in vitro stimulation have been traced for
the four most prominent influenza peptides through primary and
secondary responses into long-term memory. The
DbNP366 epitope that is immunodominant after
the H3N2 H1N1 challenge shows the lowest frequencies of
CD8+ IFN-+TNF-+ cells for >6
wk, and the intensity of IFN- staining is also low for the first 3
wk. By 11 wk, however, the IFN-/TNF- profiles look to be similar
for all four epitopes. At least by the criterion of cytokine
production, there is considerable epitope-related functional diversity
in the influenza virus-specific CD8+ T cell response. The
results for the KbPB1703 epitope and the
PB2198 mimotope also provide a cautionary tale for those
using the cytokine staining approach to identity antigenic
peptides.
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S. R. Crowe, S. J. Turner, S. C. Miller, A. D. Roberts, R. A. Rappolo, P. C. Doherty, K. H. Ely, and D. L. Woodland Differential Antigen Presentation Regulates the Changing Patterns of CD8+ T Cell Immunodominance in Primary and Secondary Influenza Virus Infections J. Exp. Med., August 4, 2003; 198(3): 399 - 410. [Abstract] [Full Text] [PDF]
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R. J. Webby, S. Andreansky, J. Stambas, J. E. Rehg, R. G. Webster, P. C. Doherty, and S. J. Turner Protection and compensation in the influenza virus-specific CD8+ T cell response PNAS, June 10, 2003; 100(12): 7235 - 7240. [Abstract] [Full Text] [PDF]
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B. J. Johnson, E. O. Costelloe, D. R. Fitzpatrick, J. B. A. G. Haanen, T. N. M. Schumacher, L. E. Brown, and A. Kelso Single-cell perforin and granzyme expression reveals the anatomical localization of effector CD8+ T cells in influenza virus-infected mice PNAS, March 4, 2003; 100(5): 2657 - 2662. [Abstract] [Full Text] [PDF]
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K. H. Ely, L. S. Cauley, A. D. Roberts, J. W. Brennan, T. Cookenham, and D. L. Woodland Nonspecific Recruitment of Memory CD8+ T Cells to the Lung Airways During Respiratory Virus Infections J. Immunol., February 1, 2003; 170(3): 1423 - 1429. [Abstract] [Full Text] [PDF]
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P. M. Gray, G. D. Parks, and M. A. Alexander-Miller High Avidity CD8+ T Cells Are the Initial Population Elicited Following Viral Infection of the Respiratory Tract J. Immunol., January 1, 2003; 170(1): 174 - 181. [Abstract] [Full Text] [PDF]
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S. Tourdot and K. G. Gould Competition Between MHC Class I Alleles for Cell Surface Expression Alters CTL Responses to Influenza A Virus J. Immunol., November 15, 2002; 169(10): 5615 - 5621. [Abstract] [Full Text] [PDF]
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L. A. Zenewicz, K. E. Foulds, J. Jiang, X. Fan, and H. Shen Nonsecreted Bacterial Proteins Induce Recall CD8 T Cell Responses But Do Not Serve as Protective Antigens J. Immunol., November 15, 2002; 169(10): 5805 - 5812. [Abstract] [Full Text] [PDF]
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G. T. Belz, D. Wodarz, G. Diaz, M. A. Nowak, and P. C. Doherty Compromised Influenza Virus-Specific CD8+-T-Cell Memory in CD4+-T-Cell-Deficient Mice J. Virol., October 25, 2002; 76(23): 12388 - 12393. [Abstract] [Full Text] [PDF]
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H. Wedemeyer, X.-S. He, M. Nascimbeni, A. R. Davis, H. B. Greenberg, J. H. Hoofnagle, T. J. Liang, H. Alter, and B. Rehermann Impaired Effector Function of Hepatitis C Virus-Specific CD8+ T Cells in Chronic Hepatitis C Virus Infection J. Immunol., September 15, 2002; 169(6): 3447 - 3458. [Abstract] [Full Text] [PDF]
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W. Chen, J. R. Bennink, P. A. Morton, and J. W. Yewdell Mice Deficient in Perforin, CD4+ T Cells, or CD28-Mediated Signaling Maintain the Typical Immunodominance Hierarchies of CD8+ T-Cell Responses to Influenza Virus J. Virol., September 11, 2002; 76(20): 10332 - 10337. [Abstract] [Full Text] [PDF]
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K.-Y. Lee, E. Chun, N.-Y. Kim, and B. L. Seong Characterization of HLA-A2.1-restricted epitopes, conserved in both Hantaan and Sin Nombre viruses, in Hantaan virus-infected patients J. Gen. Virol., May 1, 2002; 83(5): 1131 - 1136. [Abstract] [Full Text] [PDF]
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H. Liu, S. Andreansky, G. Diaz, T. Hogg, and P. C. Doherty Reduced Functional Capacity of CD8+ T Cells Expanded by Post-Exposure Vaccination of {gamma}-Herpesvirus-Infected CD4-Deficient Mice J. Immunol., April 1, 2002; 168(7): 3477 - 3483. [Abstract] [Full Text] [PDF]
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A. C. M. Boon, G. de Mutsert, Y. M. F. Graus, R. A. M. Fouchier, K. Sintnicolaas, A. D. M. E. Osterhaus, and G. F. Rimmelzwaan 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., January 15, 2002; 76(2): 582 - 590. [Abstract] [Full Text] [PDF]
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J. A. Wiley, R. J. Hogan, D. L. Woodland, and A. G. Harmsen Antigen-Specific CD8+ T Cells Persist in the Upper Respiratory Tract Following Influenza Virus Infection J. Immunol., September 15, 2001; 167(6): 3293 - 3299. [Abstract] [Full Text] [PDF]
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J. M. Riberdy, A. Zirkel, S. Surman, J. L. Hurwitz, and P. C. Doherty Cutting Edge: Culture with High Doses of Viral Peptide Induces Previously Unprimed CD8+ T Cells to Produce Cytokine J. Immunol., September 1, 2001; 167(5): 2437 - 2440. [Abstract] [Full Text] [PDF]
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S. J. Turner, R. Cross, W. Xie, and P. C. Doherty Concurrent Naive and Memory CD8+ T Cell Responses to an Influenza A Virus J. Immunol., September 1, 2001; 167(5): 2753 - 2758. [Abstract] [Full Text] [PDF]
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