Addition of a prominent epitope affects influenza A virus-specific CD8 + T cell immunodominance hierarchies when antigen is limiting

Misty Rayna Jenkins, Richard Webby, Peter C. Doherty, Stephen J. Turner

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A reverse genetics strategy was used to insert the OVA peptide (amino acid sequence SIINFEKL; OVA 257-264 ) into the neuraminidase stalk of both the A/PR8 (H1N1) and A/HK×31 (H3N2) influenza A viruses. Initial characterization determined that K b OVA 257 is presented on targets infected with PR8-OVA and HK-OVA without significantly altering D b nucleoprotein (NP) 366 presentation. There were similar levels of K b OVA 257 - and D b NP 366 -specific CTL expansion following both primary and secondary intranasal challenge. Interestingly, while variable, the presence of the immunodominant K b OVA 257 -specific response resulted in diminished D b acidic polymerase 224 - and K b basic polymerase subunit I 703 -, but not D b NP 366 -SpCCiSc responses and didn't alter endogenous influenza A virus-specific immunodominance hierarchies. However, challenging PR8-OVA-primed mice with HK-OVA via the i.p. route, and thereby limiting Ag dose, led to a reduction in the magnitude of all the influenza A virus-specific responses measured. A similar reduction in CTL response to native epitopes was also seen following primary respiratory HK-OVA infection of mice that received substantial numbers of K b OVA 257 -specific TCR transgenic T cells. Thus, during the course of infection, the generation of individual virus-specific CTL responses is independently regulated. However, in cases in which Ag is limiting, or high precursor frequency, the presence of immunodominant CTL responses can impact on the magnitude of other specific populations. Therefore, depending on both the size of the T cell precursor pool and the mode of Ag presentation, the addition of a major epitope can diminish the size of endogenous, influenza-specific CD8 + T cell responses, although never to the point that these are totally compromised.

Original languageEnglish
Pages (from-to)2917-2925
Number of pages9
JournalJournal of Immunology
Issue number5
Publication statusPublished - 1 Sep 2006
Externally publishedYes

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