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

    21 Citations (Scopus)


    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
    Issue numberOCT
    Publication statusPublished - 2015


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


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