TY - JOUR
T1 - NK cell killer Ig-like receptor repertoire acquisition and maturation are strongly modulated by HLA class i molecules
AU - Sleiman, Marwan
AU - Brons, Nicolaas H.C.
AU - Kaoma, Tony
AU - Dogu, Figen
AU - Villa-Forte, Alexandra
AU - Lenoble, Patrick
AU - Hentges, François
AU - Kotsch, Katja
AU - Gadola, Stephan D.
AU - Vilches, Carlos
AU - Zimmer, Jacques
PY - 2014/3/15
Y1 - 2014/3/15
N2 - The interaction between clonally distributed inhibitory receptors and their activating counterparts on NK cells and HLA class I molecules defines NK cell functions, but the role of HLA class I ligands in the acquisition of their receptors during NK development is still unclear. Although some studies demonstrated that HLA-C affects the expression of killer Ig-like receptors (KIR), other studies showed that NK cells acquire their KIR repertoire in a stochastic manner. Only when infected with human CMV is an expansion of self-specific KIR+ NKG2C+ NK cells detected. To gain more insight into this question, we compared the coexpression of different KIR molecules, NKG2A, CD8, and CD57, on NK cells in healthy donors and seven patients with deficient HLA class I expression due to mutations in one of the TAP genes. Our results show a correlation between the presence/absence of HLA class I molecules and the coexpression of their receptors. In an HLA class I low-expression context, an increase in KIR molecules' coexpression is detected on the NKG2A+ CD8+ subset. In functional assays, hyporesponsiveness was observed for TAPdeficient NK cells derived from four patients. In contrast, NK cells from patient five were functional, whereas CD107a+ and IFN-γ+ CD56dim NK cells presented a different pattern of HLA class I receptors compared with healthy donors. Taken together, our results provide strong evidence for the role of HLA class I molecules in NK cell maturation and KIR repertoire acquisition. The Journal of Immunology, 2014, 192: 2602-2610.
AB - The interaction between clonally distributed inhibitory receptors and their activating counterparts on NK cells and HLA class I molecules defines NK cell functions, but the role of HLA class I ligands in the acquisition of their receptors during NK development is still unclear. Although some studies demonstrated that HLA-C affects the expression of killer Ig-like receptors (KIR), other studies showed that NK cells acquire their KIR repertoire in a stochastic manner. Only when infected with human CMV is an expansion of self-specific KIR+ NKG2C+ NK cells detected. To gain more insight into this question, we compared the coexpression of different KIR molecules, NKG2A, CD8, and CD57, on NK cells in healthy donors and seven patients with deficient HLA class I expression due to mutations in one of the TAP genes. Our results show a correlation between the presence/absence of HLA class I molecules and the coexpression of their receptors. In an HLA class I low-expression context, an increase in KIR molecules' coexpression is detected on the NKG2A+ CD8+ subset. In functional assays, hyporesponsiveness was observed for TAPdeficient NK cells derived from four patients. In contrast, NK cells from patient five were functional, whereas CD107a+ and IFN-γ+ CD56dim NK cells presented a different pattern of HLA class I receptors compared with healthy donors. Taken together, our results provide strong evidence for the role of HLA class I molecules in NK cell maturation and KIR repertoire acquisition. The Journal of Immunology, 2014, 192: 2602-2610.
UR - http://www.scopus.com/inward/record.url?scp=84897516795&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1302843
DO - 10.4049/jimmunol.1302843
M3 - Article
C2 - 24554773
AN - SCOPUS:84897516795
SN - 0022-1767
VL - 192
SP - 2602
EP - 2610
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -