The balance in KIR/NKG2A expression is determined by the number of strong KIR-HLA interactions and results in equilibrium of total NK-cell repertoire response. (A) For the donor panel, the ratio in the frequency of NK cells that lack NKG2A (sum of the null subset and the NKG2A⁻KIR⁺ subset) to NK cells that have NKG2A is plotted against the number of strong ligands. All C2, Cw*07, Cw*12, B*46, and all Bw4⁺ HLA-B allotypes, with the exception of B*13 were considered strong ligands, but to NK cells that have NKG2A in donors having the cognate inhibitory KIR. The mean ratio (2.4) for the panel is given by the horizontal dotted line. Ratios greater than the mean represent repertoires dominated by KIR (KIR-dominant) and ratios below the mean represent repertoires dominated by NKG2A (NKG2A-dominant). The correlation of KIR-dominant repertoires with one ligand and of NKG2A-dominant repertoires with 2 or more ligands was significant. *P < .05. (B) Comparison of the ratio of the expression frequencies of KIR2DL3 and NKG2A with the ratio of their enhanced missing-self responses. Closed symbols represent donors having strong KIR3DL1 and/or 2DL1 responses; open symbols represent donors with weak 3DL1 and 2DL1 responses. Between receptor expression and response, 4 patterns were discerned. On the right side of the panel are donors with a stronger response of 2DL3 over NKG2A and either strong (●) or weak (○) KIR3DL1 and/or 2DL1 responses. On the left side are donors with stronger response of NKG2A over 2DL3 and either strong (▴) or weak (Δ) 3DL1 and 2DL1 responses. (C) The relative proportions of 5 NK subsets in 5 donors (Figure 3E) representing the 5 types of NK-cell repertoire. The type 1 repertoire is characterized by a larger subset of NK cells coexpressing inhibitory KIR, type 2 by receptor-null cells, type 3 by cells expressing single inhibitory KIR, type 4 by cells coexpressing KIR and NKG2A, and type 5 by a higher proportion of single-positive NKG2A cells compared with coexpression of NKG2A with KIR. (D) Overall levels of enhancement in missing-self response of 58 NK-cell repertoires. The donors are grouped according to the 5 repertoire types and plotted according to the sum of the enhanced response for all receptors having a cognate ligand. The type 2 null-dominant repertoires have a significantly lower enhanced response with a mean of 13 compared with 22, 20, 22, and 16 for the type 1, 3, 4, and 5 repertoires, respectively (P < .005). The summed enhanced response for the donors was less than 35 (dotted horizontal line) with one exception. *P < .05. ***P < .005.