HLA-C epitopes impact NKG2A expression and NK cell function. (A) NKG2A⁺ NK cell frequency and MFI stratified by the SNP rs2734440 in 400 healthy blood donors. (B) NKG2A⁺ NK cell frequency and NKG2A MFI stratified by the HLA-C KIR ligand epitope and HCMV serostatus. (C) NKG2A⁺ NK cell frequency and MFI stratified by HLA-C epitope, NKG2A SNP genotype, and HCMV serostatus. (D) Degranulation response of NKG2A-SP CD56^dim NK cells to K562 HLA-E KO segregated by HLA-C KIR ligand epitope. (E) Global NK inhibition in C1/C1 and C2/C2 in HCMV⁺ individuals with the NKG2A 440C/C (high) genotype, as measured by change in CD107a response to K562 HLA-E KO vs K562 transduced with HLA-E. For panels, A-C,E, t tests were performed, and mean ± SEM is presented to analyze NKG2A frequencies. Mann-Whitney tests were performed and median ± IQRs are presented to analyze NKG2A MFI for panels A-C. Symbols represent individual samples. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001.