Granzyme B loading is genetically hardwired and stable over time. (A) Dot plot representing the delta of granzyme B loading in either repeated samplings (sampling 1 vs sampling 2) or random pairing, calculated as the difference in granzyme B content between 2 randomly selected donors (donor pair) with the indicated genotype. (B) Granzyme B content of educated NK cells/Nil NK cells is shown for each donor and stratified based on the HLA-C background, either C1/C1, C1/C2 or Bw4. Each dot represents 1 donor, and bars show the median. Identification of donors with very high granzyme B content in their NK cells based on the interquartile range rule (outliers in red, blue or green). (C) Allelic distribution in KIR2DL3 granzyme B^high donors (n = 9) compared with other C1C1 donors (n = 148). (D) Allelic distribution KIR2DL3⁺ and KIR2DL1⁺ granzyme B^high donors (n = 12 and n = 4, respectively) among C1/C2 donors, compared with other C1/C2 donors (n = 110). (E) Allelic distribution in KIR3DL1⁺ granzyme B^high donors (n = 11) among Bw4⁺ donors compared with other Bw4⁺ donors (n = 159). One-way ANOVA tests followed by Kruskal-Wallis multiple comparison tests were performed. (D-F) The pie charts represent the frequencies of donors with specific HLA-C or Bw4 alleles in the outlier population and in the general population. The outliers are identified with the interquartile range formula. Χ tests were performed. ∗∗∗∗P < .0001; ∗∗∗P < .001; ∗∗P <.01; and ∗P < .05.