A Previously Unrecognized H-2Db-Restricted Peptide Prominent in the Primary Influenza A Virus-Specific CD8+ T-Cell Response Is Much Less Apparent following Secondary Challenge

doi:10.1128/JVI.74.8.3486-3493.2000

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Journal of Virology, April 2000, p. 3486-3493, Vol. 74, No. 8
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Previously Unrecognized H-2D^b-Restricted Peptide Prominent in the Primary Influenza A Virus-Specific CD8⁺ T-Cell Response Is Much Less Apparent following Secondary Challenge

Gabrielle T. Belz,¹ Weidong Xie,¹ John D. Altman,² and Peter C. Doherty¹^,^*

Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee,¹ and Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia²

Received 16 November 1999/Accepted 18 January 2000

Respiratory challenge of H-2^b mice with an H3N2 influenza A virus causes an acute, transient pneumonitis characterized by themassive infiltration of CD8⁺ T lymphocytes. The inflammatory process monitored by quantitativeanalysis of lymphocyte populations recovered by bronchoalveolarlavage is greatly enhanced by prior exposure to an H1N1 virus,with the recall of cross-reactive CD8⁺-T-cell memory leading to more rapid clearance of the infectionfrom the lungs. The predominant epitope recognized by the influenzavirus-specific CD8⁺ set has long been thought to be a nucleoprotein (NP_366-374)presented by H-2D^b (D^bNP₃₆₆). This continues to be true for the secondary H3N2 $right-arrow$ H1N1challenge but can no longer be considered the case for the primaryresponse to either virus. Quantitative analysis based on intracellularstaining for gamma interferon has shown that the polymerase 2protein (PA_224-233) provides a previously undetected epitope(D^bPA₂₂₄) that is at least as prominent as D^bNP₃₆₆ during the first 10 days following primary exposure to eitherthe H3N2 or H1N1 virus. The response to D^bNP₃₆₆ seems to continue for longer, even when infectious viruscan no longer be detected, but there is no obvious differencein the prevalence of memory T cells specific for D^bNP₃₆₆ and D^bPA₂₂₄. The generalization that the magnitude of the functionalmemory T-cell pool is a direct consequence of the clonal burstsize during the primary response may no longer be useful. PreviousCD8⁺-T-cell immunodominance heirarchies defined largely by cytotoxicT-lymphocyte assays may need to berevised.

^* Corresponding author. Mailing address: Department of Immunology, St. Jude Children's Research Hospital, 332 N. Lauderdale,Memphis, TN 38105. Phone: (901) 495-3470. Fax: (901) 495-3107.E-mail: peter.doherty{at}stjude.org.

Journal of Virology, April 2000, p. 3486-3493, Vol. 74, No. 8
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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