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Nat.Com. Quantification of epitope abundance reveals the effect of direct and cross-presentation on influenza CTL responses

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  • Nat.Com. Quantification of epitope abundance reveals the effect of direct and cross-presentation on influenza CTL responses

    Nat Commun. 2019 Jun 28;10(1):2846. doi: 10.1038/s41467-019-10661-8.
    Quantification of epitope abundance reveals the effect of direct and cross-presentation on influenza CTL responses.

    Wu T1, Guan J1, Handel A2, Tscharke DC3, Sidney J4, Sette A4,5, Wakim LM6, Sng XYX1, Thomas PG7, Croft NP8, Purcell AW9, La Gruta NL10,11.
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    Abstract

    The magnitude of T cell responses to infection is a function of the na?ve T cell repertoire combined with the context and duration of antigen presentation. Using mass spectrometry, we identify and quantify 21 class 1 MHC-restricted influenza A virus (IAV)-peptides following either direct or cross-presentation. All these peptides, including seven novel epitopes, elicit T cell responses in infected C57BL/6 mice. Directly presented IAV epitopes maintain their relative abundance across distinct cell types and reveal a broad range of epitope abundances. In contrast, cross-presented epitopes are more uniform in abundance. We observe a clear disparity in the abundance of the two key immunodominant IAV antigens, wherein direct infection drives optimal nucleoprotein (NP)366-374 presentation, while cross-presentation is optimal for acid polymerase (PA)224-233 presentation. The study demonstrates how assessment of epitope abundance in both modes of antigen presentation is necessary to fully understand the immunogenicity and response magnitude to T cell epitopes.


    PMID: 31253788 PMCID: PMC6599079 DOI: 10.1038/s41467-019-10661-8
    Free PMC Article
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