Frontiers in Immunology (Oct 2015)

Polyclonal Expansion of NKG2C+ NK Cells in TAP-deficient Patients

  • vivien eBeziat,
  • vivien eBeziat,
  • Marwan eSleiman,
  • Jodie eGoodridge,
  • Jodie eGoodridge,
  • Mari eKaarbo,
  • lisa eliu,
  • Halvor eRollag,
  • hans-gustaf eljunggren,
  • jacques ezimmer,
  • Karl-Johan eMalmberg,
  • Karl-Johan eMalmberg

DOI
https://doi.org/10.3389/fimmu.2015.00507
Journal volume & issue
Vol. 6

Abstract

Read online

Adaptive natural killer (NK) cell responses to human cytomegalovirus (CMV) 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 expansion of NKG2C+ NK cells in patients with transporter associated with antigen presentation (TAP)-deficiency, whom 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. Thus, the emergence of NKG2C-responsive adaptive NK cells in TAP-deficient patients may contribute to anti-viral immunity and potentially explain these patients’ low incidence of severe viral infections.

Keywords