NK subset frequencies in human NK-cell repertoires vary in their amount of departure from the product rule. (A) For each donor, the deviation of the observed NK-cell repertoire from the product rule was assessed for 5 parameters: single KIR expression (▴), KIR-KIR coexpression (■), NKG2A expression alone (○), NKG2A-KIR coexpression (▵), and no receptor expression (●). The donors are ordered from left to right according to decreasing deviation in single KIR expression. (B) KIR coexpression is higher than expectation under the product rule regardless of ligand presence. The amount of deviation from expectations under the product rule is shown for NK subsets coexpressing 2 KIR (2DL1-2DL3, 2DL3-3DL1, 3DL1-2DL1). This amount is shown separately by the number of cognate ligands (0-2) for the 2 KIR. The deviations are all positive in these subsets from donors with type 1, 2, 4, and 5 repertoires. The deviations display a different pattern for cells from donors with type 3 repertoires, where KIR coexpression is drastically reduced from frequencies predicted under stochastic coexpression, but only in those subsets that have developed in the presence of autologous cognate ligands. All donors are group A homozygotes. Donors for type 1, 2, 4, and 5 repertoires: n = 24; those for type 3 repertoires: n = 5. (C) KIR coexpression is enhanced when multiple KIR confer similar levels of enhanced missing-self response. The ratio of missing-self response between KIR with the strongest response and that from the second strongest are compared in donors with type 1 (●, n = 7) and type 3 (○, n = 8) repertoires. The plots display an association with the amount of deviation in KIR-KIR coexpression.