Composition and dynamics of the uterine NK cell KIR repertoire in menstrual blood

Uterine natural killer (NK) cells are abundantly present in endometrium and decidua. Their function is governed by interactions between killer cell immunoglobulin-like receptors (KIRs) and cognate human leukocyte antigen (HLA) class I ligands. These interactions have implications for reproductive success. Whereas most uterine NK cells are known to express KIRs, little information is available about KIR repertoire formation and stability over time. This is primarily due to inherent difficulties in gaining access to human uterine tissue. As endometrial immune cells are shed during menstruation, menstrual blood may serve as a source for studies of KIRs on uterine NK cells. Here, we performed a combined assessment of six inhibitory and activating KIRs on uterine NK cells from paired menstrual and peripheral blood. Menstrual blood contained a high frequency of uterine NK cells expressing KIRs. The uterine NK cell KIR repertoires were markedly different from those in peripheral blood NK cells, biased toward KIR2D-receptor expression, and formed independently of selection conferred by cognate HLA class I molecules. Moreover, uterine NKG2C⁺self-KIR⁺ NK cell expansions were detected. Finally, the distinct KIR repertoires of uterine NK cells were stable over multiple menstrual cycles. Our results provide novel insight into KIR repertoire formation on human uterine NK cells.