Autologous and allogeneic HLA KIR ligand environments and activating KIR control KIR NK‐cell functions

Abstract

cancérologie, UMR892, UFR Médecine et Techniques médicales, Nantes, France NK-cell function is regulated by a balance between inhibitory and activating killer cell immunoglobulin-like receptors (KIR) that specifically recognize HLA class I molecules. Using KIR-specific mAb to discriminate between KIR2DS1 and KIR2DL1 receptors, we show that KIR2DS1 + NK cells are C2-alloreactive only from C2 À individuals. Moreover, using an in vitro model of NK-cell expansion, we show here that the frequency of KIR2DL1 + NK cells is significantly higher in the absence of C2 ligand on stimulator EBV-B cells than in its presence. This observation was made regardless of the presence or absence of the autologous C2 ligand, suggesting that the C2 À EBV-B stimulator cells used in this in vitro model could activate unlicensed KIR2DL1 + NK cells. In the case of KIR2DL1 + /S1 + genotyped individuals, KIR2DS1 + NK-cell frequency was increased after stimulation with C2 + compared with C2 À stimulator B cells, but only from C2 À individuals. Altogether, these data highlight the C2 alloreactivity of KIR2DS1 + NK cells that is only observed in C2 À individuals. These results provide new insights into the way in which NK KIR cell expansion might be regulated in an allogeneic environment.

Phenotypic and Functional Analyses of KIR3DL1+ and KIR3DS1+ NK Cell Subsets Demonstrate Differential Regulation by Bw4 Molecules and Induced KIR3DS1 Expression on Stimulated NK Cells

“…Finally, although in the KIR2DL1/KIR2DS1 pair only one of these two homologous receptors can be functional, depending on the presence or absence of HLA-C2 ligand (36), the KIR3DL1 and KIR3DS1 receptors do not act in the same way. In fact, KIR3DL1…”

“…FEB and DAX, both principal EBV-B cell lines used in the study, were obtained from two different HLA-typed blood donors: FEB (HLA-A*01-*01; -B*08 -*08; -Cw*07 -*07) and DAX (HLA-A*02 -*03; -B*44 -*44; -Cw*05 -*05). B cells were isolated from PBMCs obtained from healthy individuals as described previously (36). HLA class-I deficient 721.221 lymphoblastoid EBV-B cells, referred to as 221 cells, and HLA class I-deficient immortalized myelogenous leukemia line K562 were used as controls in functional assays.…”

“…Amplification of NK cells was evaluated using an in vitro model based on a protocol described previously (36 …”

Amplified NKG2C+ NK Cells in Cytomegalovirus (CMV) Infection Preferentially Express Killer Cell Ig-like Receptor 2DL: Functional Impact in Controlling CMV-Infected Dendritic Cells

“…PBMCs were isolated as previously described (24,25). Thereafter, NK cells were amplified after in vitro stimulation with irradiated C1 + and C2…”

Future directions of clinical laboratory evaluation of pregnancy

“…62 It is known that KIR2DS1/HLA-C2 receptor/ligand interaction contributes to functional NK cell education; KIR2DS1pos NK cells from C2 negative individual demonstrated strong alloreactive activity against HLA-C2 targets, in contrast to low or absent alloreactivity if the NK cells were from a C2-positive individual. 63,64 Additional studies would be helpful to evaluate whether there is a genetic susceptibility to RPL in KIR2DS1/HLA-C2 co-expression cases.…”