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Abstract: EP1265

Type: E-Poster Presentation

Session title: Stem cell transplantation - Clinical

Background
NK education plays a vital role in leukemia control and infection prevention after hematopoietic stem cell transplantation（HSCT）, which is affected by interaction of human leukocyte antigen (HLA)-I/killer immunoglobulin receptor（KIR). However, different HLA-I/KIR interactions on NK education for intrinsic responsiveness is still conflicting. Recent studies showed that obvious NKG2C+ NK cell expansions are dominated by specific single KIR clones, mainly encoded by the centromeric part of group A haplotypes under cytomegalovirus (CMV) infection. However, the effect of HLA-I/KIR interactions on NKG2C+ NK education post HSCT were still unknown.

Aims
To figure out what KIR/HLA-I interaction has a main effect on the expansion and reactivity of NKG2C+ NK cells in NK education after HSCT. 

Methods
We prospectively studied 114 patients with malignant hematologic disease who underwent HSCT at the Peking University People’s Hospital between May 2016 and April 2017. All patients and donors provided written informed consent. Patient and donor DNA was prepared from peripheral blood mononuclear cells (PBMCs) for HLA, NKG2C and KIR genotyping test.The expansion, expression of cell surface molecules and function of three single KIR positive/NKG2C+ NK cells (KIR2DL1, KIR2DL2/L3 and KIR3DL1) at day 30, 90 and 180 are tested by flow cytometric analyses and cytotoxicity assays. Statistical analysis was performed by nonparametric test, Pearson correlation test and Chi-squared Test.

Results
It was shown that KIR2DL2/L3 single positive NKG2C+ cells significantly expanded in NKG2C+ NK cells than KIR2DL1 and KIR3DL1, in group1 where donor and recipient were both HLA- C1C1, and group2 where donor and recipient are both HLA -C1BW4, at day 90 (group1:P<0.0001, P=0.0001; group2:P<0.0001, P=0.0232) and 180(group1:P<0.0001; group2:P=0.0003, P=0.2581).  In group3, where donor and recipient are both HLA-C1C2BW4, the proportion of KIR2DL2/L3 and KIR2DL1 single positive/NKG2C+ were both higher than KIR3DL1 (Day90:P<0.0001, P=0.0023; Day180:P<0.0001, P=0.0007). MFI of NKp30 expression on KIR2DL2/L3 single positive/NKG2C+ NK cells was significantly higher than KIR2DL1/NKG2C+ and KIR3DL1/NKG2C+, in group1, group2 and group3. Additionally, we found that KIR2DL2/L3 single positive cells showed more significant proliferation in NKG2C+ NK cells than NKG2A- NK cells at day 30, 90 and 180. NKG2C genotype (NKG2C^wt/del or NKG2C^wt/wt ) of donor cells had no effect on the significant expansion of KIR2DL2/L3 single positive/NKG2C+ NK cells at day 30, 90 and 180. Moreover, we observed that KIR CenA/A genotype may induce strong expansion of NKG2C+ NK cells and KIR2DL2/L3 single positive/NKG2C+ NK cells. Besides, it was observed that the frequencies of KIR2DL2/L3 single positive/NKG2C+ NK cells showed significant consistent correlation with the proportion of NKG2C+ NK cells among NK cells only at day 90 (P=0.0417). However, the proportion of KIR2DL2/L3/NKG2C+ was irrelevant with CMV infection type (refractory reactivation or not), clinical outcomes (relapse or not ) and duration of viremia . Finally, the data revealed that the number of KIRs and KIR ligands shared by donors and recipients has no effect on NKG2C+ NK cells.

Conclusion
Interaction between KIR and HLA-C can modulate the education of NKG2C+ NK cells, characterized by KIR2DL2/L3 single positive/NKG2C+ NK cells clonal expansion, with NKp30 increasing expression, dominated by the combination of KIR2DL2/L3 and HLA-C1.

Keyword(s): HLA, KIR, NK cell, NK receptor