TY - JOUR
T1 - Polyclonal expansion of NKG2C+ NK cells in TAP-deficient patients
AU - Béziat, Vivien
AU - Sleiman, Marwan
AU - Goodridge, Jodie P.
AU - Kaarbo, Mari
AU - Liu, Lisa L.
AU - Rollag, Halvor
AU - Ljunggren, Hans Gustaf
AU - Zimmer, Jacques
AU - Malmberg, Karl Johan
N1 - Publisher Copyright:
© 2015 Béziat, Sleiman, Goodridge, Kaarbø, Liu, Rollag, Ljunggren, Zimmer and Malmberg.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Adaptive immunity
KW - Cytomegalovirus infections
KW - Killer cell immunoglobulin-like receptor
KW - Natural killer cells
KW - Transporter associated with antigen processing
UR - http://www.scopus.com/inward/record.url?scp=84946550228&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2015.00507
DO - 10.3389/fimmu.2015.00507
M3 - Article
AN - SCOPUS:84946550228
SN - 1664-3224
VL - 6
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - OCT
M1 - 507
ER -