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NKG2C+ natural killer (NK) cell plays a vital role in CMV infection control after hematopoietic stem cell transplantation (HSCT). However, the modulation on NKG2C+ NK cell reconstitution is still unclear. NK cell education is affected by the interactions of HLA-I/killer immunoglobulin receptor (KIR). Our aim is to figure out which HLA-I/KIR interaction plays a dominant role in NKG2C+ NK education. Based on allogeneic haploidentical HSCT, we investigated the expansion and function of single KIR positive NKG2C+ NK cells  via  the interaction of KIR with both donor HLA and recipient HLA at days 30, 90, and 180 after HSCT. KIR2DL2/L3 single-positive/NKG2C +  cells were significantly expanded compared with KIR2DL1 or KIR3DL1 single-positive/NKG2C +  cells when donors and recipients were both HLA-C1/C1 or HLA-C1C1BW4 ( p  &amp;lt; 0.05), with higher NKp30 expression ( p  &amp;lt; 0.05). Moreover, the proportion of single KIR positive NK cells increased in both NKG2C + /NKG2A -  NK cells and conventional NKG2C - /NKG2A -  NK cells over time. We also observed that increased proportion of KIR2DL2/L3 single-positive/NKG2C +  NK cells correlated with higher incidence of acute graft-versus-host disease (aGVHD). Our study allows a better understanding of HLA-I/KIR interaction in the NKG2C+ NK cell education after HSCT.

frontiers in immunology

The Interaction of HLA-C1/KIR2DL2/L3 Promoted KIR2DL2/L3 Single-Positive/NKG2C-Positive Natural Killer Cell Reconstitution, Raising the Incidence of aGVHD after Hematopoietic Stem Cell Transplantation