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Response to Comment on “Frequency of Epitope-Specific Naive CD4+ T Cells Correlates with Immunodominance in the Human Memory Repertoire”

William W. Kwok and Eddie A. James
J Immunol June 1, 2012, 188 (11) 5206; DOI: https://doi.org/10.4049/jimmunol.1290019
William W. Kwok
Benaroya Research Institute at Virginia Mason, Seattle, WA 98101
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Eddie A. James
Benaroya Research Institute at Virginia Mason, Seattle, WA 98101
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We appreciate the comments of Ascough et al. concerning the relevance of immunodominant protective Ag (PA) epitopes that were recently reported by our group (1). We find it equally gratifying that T cell specificities, which were prevalent in the naive repertoire of unvaccinated subjects and the memory repertoire of vaccinated subjects, were also part of the natural immune response towards PA, as such naturally infected subjects were not available for our study. Given the complex regulation of PA and other anthrax toxin genes, differences between the responses of vaccinees and patients would certainly be plausible (2, 3).

We agree that responses to these three peptides are likely to be relevant for a wide section of the population. As summarized in Table I, we have demonstrated using tetramer-guided epitope mapping that these peptides do contain epitopes that are presented and recognized in the context of several common HLA-DR alleles. These observations are in general agreement with the binding affinities observed by Ascough et al. While binding of a given epitope to a particular HLA-DR protein is not a guarantee that it will be recognized in that context, the correlation between these data sets indicates that such binding measurements do have predictive utility.

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Table I. PA-specific T cell responses in anthrax vaccine adsorbed vaccinees for several common HLA-DR alleles, identified by tetramer-guided epitope mapping
  • Copyright © 2012 by The American Association of Immunologists, Inc.

References

  1. ↵
    1. Kwok W. W.,
    2. V. Tan,
    3. L. Gillette,
    4. C. T. Littell,
    5. M. A. Soltis,
    6. R. B. LaFond,
    7. J. Yang,
    8. E. A. James,
    9. J. H. DeLong
    . 2012. Frequency of epitope-specific naïve CD4+ T cells correlates with immunodominance in the human memory repertoire. J. Immunol. 188: 2537–2544.
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Brossier F.,
    2. M. Mock
    . 2001. Toxins of Bacillus anthracis. Toxicon 39: 1747–1755.
    OpenUrlCrossRefPubMed
  3. ↵
    1. Koehler T. M.
    2002. Bacillus anthracis genetics and virulence gene regulation. Curr. Top. Microbiol. Immunol. 271: 143–164.
    OpenUrlPubMed
    1. Kwok W. W.,
    2. J. Yang,
    3. E. James,
    4. J. Bui,
    5. L. Huston,
    6. A. R. Wiesen,
    7. M. Roti
    . 2008. The anthrax vaccine adsorbed vaccine generates protective antigen (PA)-specific CD4+ T cells with a phenotype distinct from that of naïve PA T cells. Infect. Immun. 76: 4538–4545.
    OpenUrlAbstract/FREE Full Text
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The Journal of Immunology: 188 (11)
The Journal of Immunology
Vol. 188, Issue 11
1 Jun 2012
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Response to Comment on “Frequency of Epitope-Specific Naive CD4+ T Cells Correlates with Immunodominance in the Human Memory Repertoire”
William W. Kwok, Eddie A. James
The Journal of Immunology June 1, 2012, 188 (11) 5206; DOI: 10.4049/jimmunol.1290019

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Response to Comment on “Frequency of Epitope-Specific Naive CD4+ T Cells Correlates with Immunodominance in the Human Memory Repertoire”
William W. Kwok, Eddie A. James
The Journal of Immunology June 1, 2012, 188 (11) 5206; DOI: 10.4049/jimmunol.1290019
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