Differential contribution of education through KIR2DL1, KIR2DL3, and KIR3DL1 to antibody-dependent (AD) NK cell activation and ADCC

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Irene Lisovsky¹  Sanket Kant¹  Alexandra Tremblay-McLean¹  Gamze Isitman¹  Zahra Kiani¹  Franck P. Dupuy¹  Louise Gilbert¹  Julie Bruneau³  Naglaa H. Shoukry³  Bertrand Lebouché¹  Nicole F. Bernard¹ 

[1] Research Institute of the McGill University Health Center (RI-MUHC);Division of Experimental Medicine, McGill University;Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM);Department of Family and Emergency Medicine, Université de Montréal;Department of Family Medicine, McGill University;McGill University Health Centre;Division of Clinical Immunology, McGill University Health Centre

关键词: ADCC;    Ab-dependent NK cell activation;    KIR;    NK cell education;    NKG2A;   

DOI  :  10.1002/JLB.4A0617-242RRR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The engagement of activating NK receptors (aNKR) stimulates NK cell activity, provided that interactions between inhibitory NK receptors (iNKR) with their HLA ligands do not override them. Abs bound to target cells can also activate NK cells by engaging the CD16 aNKR. NK cell education status is an important factor for Ab-dependent NK cell activation (ADNKA) of some NK cell subsets. However, whether NK cell education also influences Ab-dependent cellular cytotoxicity (ADCC) levels is not fully known. ADCC-GranToxiLux (GTL) assays measured ADCC activity as the frequency of granzyme B positive (%GzB+) target cells. Target cells were anti-HIV Immunoglobulin G (HIVIG)-opsonized CEM-NKr.CCR5 (CEM) cells. Lymphocytes and sorted single positive (SP) NKG2A+, KIR2DL1+, KIR2DL3+, and KIR3DL1+ NK cells, to self- and nonself HLA, were used as effectors in ADCC-GTL assays to examine how education status influenced ADCC activity. ADNKA activity was assessed by stimulating lymphocytes with HIVIG-opsonized CEMs and measuring the frequency of NK cell populations defined by their expression of iNKRs, along with IFN-?, CCL4, and CD107a functions. ADCC: the %GzB+ CEM cells generated by self- versus nonself HLAspecific SPiNKR did not differ. ADNKA: More NK cells educated through KIR2DL1 and KIR3DL1, but not KIR2DL3, responded to ADNKA than their uneducated counterparts. CD16 engagement induced ADCC and ADNKA activity. With the proviso that groups’ sizes were small, our results support the notion that NK cell education does not influence ADCC levels but does contribute to ADNKA activity.

【 授权许可】

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