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Journal of Virology, October 2002, p. 10332-10337, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10332-10337.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mice Deficient in Perforin, CD4+ T Cells, or CD28-Mediated Signaling Maintain the Typical Immunodominance Hierarchies of CD8+ T-Cell Responses to Influenza Virus

Weisan Chen,1,{dagger} Jack R. Bennink,1 Phillip A. Morton,2 and Jonathan W. Yewdell1*

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland,1 Discovery Research, Pharmacia, St. Louis, Missouri2

Received 18 April 2002/ Accepted 18 July 2002

CD8 T-cell (TCD8+) responses elicited by viral infection demonstrate the phenomenon of immunodominance: the numbers of TCD8+ responding to different viral peptides vary over a wide range in a reproducible manner for individuals with the same major histocompatibility complex class I alleles. To better understand immunodominance, we examined TCD8+ responses to multiple defined viral peptides following infection of mice with influenza virus. The immunodominance hierarchy of influenza virus-specific TCD8+ was not greatly perturbed by the absence of either perforin or T-helper cells or by interference with B7 (CD80)-mediated signaling. These findings indicate that costimulation by antigen-presenting cells (APCs) or killing of APCs by TCD8+ plays only a minor role in establishing the immunodominance hierarchy of antiviral TCD8+ in this system. This points to intrinsic features of the TCD8+ repertoire as major contributors to immunodominance.

* Corresponding author. Mailing address: Room 211, Bldg. 4, 4 Center Dr., MSC 0440, NIH, Bethesda, MD 20892-0440. Phone: (301) 402-4602. Fax: (301) 402-7362. E-mail: jyewdell{at}nih.gov.

{dagger} Present address: Cancer Vaccine Unit, Ludwig Institute for Cancer Research, Austin & Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia.

Journal of Virology, October 2002, p. 10332-10337, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10332-10337.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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