Polyclonal expansion of NKG2C+ NK cells in TAP-deficient patients

Vivien Béziat, Marwan Sleiman, Jodie P. Goodridge, Mari Kaarbo, Lisa L. Liu, Halvor Rollag, Hans Gustaf Ljunggren, Jacques Zimmer, Karl Johan Malmberg*

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    18 Citations (Scopus)

    Abstract

    Adaptive natural killer (NK) cell responses to human cytomegalovirus infection are characterized by the expansion of NKG2C+ NK cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs). Here, we set out to study the HLA class I dependency of such NKG2C+ NK cell expansions. We demonstrate the expansion of NKG2C+ NK cells in patients with transporter associated with antigen presentation (TAP) deficiency, who express less than 10% of normal HLA class I levels. In contrast to normal individuals, expanded NKG2C+ NK cell populations in TAP-deficient patients display a polyclonal KIR profile and remain hyporesponsive to HLA class I-negative target cells. Nonetheless, agonistic stimulation of NKG2C on NK cells from TAP-deficient patients yielded significant responses in terms of degranulation and cytokine production. Thus, while interactions with self-HLA class I molecules likely shape the KIR repertoire of expanding NKG2C+ NK cells during adaptive NK cell responses in normal individuals, they are not a prerequisite for NKG2C+ NK cell expansions to occur. The emergence of NKG2C-responsive adaptive NK cells in TAP-deficient patients may contribute to antiviral immunity and potentially explain these patients' low incidence of severe viral infections.

    Original languageEnglish
    Article number507
    JournalFrontiers in Immunology
    Volume6
    Issue numberOCT
    DOIs
    Publication statusPublished - 2015

    Keywords

    • Adaptive immunity
    • Cytomegalovirus infections
    • Killer cell immunoglobulin-like receptor
    • Natural killer cells
    • Transporter associated with antigen processing

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