A recent paper, published in Frontiers in Immunology, has found that an interaction between killer immunoglobulin-like receptors (KIRs) and HLA-C can modulate the reconstitution of natural killer group (NKG)2C+ NK cells after hematopoietic stem cell transplantation (HSCT). The authors observed increases in KIR2DL2/L3 single-positive/NKG2C+ NK cells, which correlated with a higher incidence of acute graft-versus-host disease (aGVHD).
For NK cells to function, they require a coordinated acquisition of inhibitory, activating, and adhesion signals. This process is known as “NK cell education” and includes obtaining inhibitory receptors that recognize self-HLA-I, to prevent the destruction of healthy cells. NK cell function is activated by the interaction between NK cell receptors and ligands such as KIRs and NKG2x receptors. Studies have suggested that NKG2C+ NK cells expand when stimulated by human cytomegalovirus (HCMV) and this may involve KIR family expression. This study sought to find the relationship between donor and recipient KIR ligands in NKG2C+ NK cell education in post-transplantation settings.
To examine this relationship, a cohort of 128 patients with malignant hematologic disease who underwent HSCT was monitored. Blood samples were taken for HLA, KIR, and NKG2C typing, HCMV testing, flow cytometry, and cytotoxicity assays. The authors found that KIR2DL2/L3 single-positive/NKG2C+ were significantly expanded in patients with HLA-C1/C1 or HLA-C1C1BW4 genotypes (p < 0.05), showed increased NKp30 expression (p < 0.05), and that having a strong NKG2C+ NK cell expansion was correlated with increased aGVHD incidence (p = 0.019). The authors further speculate that expanding KIR2DL2/L3+/NKG2C+ NK cells may impair the modulation of the alloreactivity of T cells in GVHD. These finding show that KIR2DL2/L3 interacts with HLA-C1 between donors and recipients to expand NKG2C+ NK cells after HSCT.
Zuo W, Yu XX, Liu XF, et al. 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. Front Immunol. 2022;13:814334. http://doi.org/10.3389/fimmu.2022.81433