Viruses that down regulate MHC expression select for degenerate KIR molecules while viruses expressing decoy molecules drive the selection of specific receptors.

<p>(A)–(B) Single representative simulations in a population infected with highly specific KIRs (i.e. bits). (A) The number of MHC molecules recognized per receptor in a population infected with an MHC down-regulating virus. The initial KIR molecules happen to recognize different numbers of MHC molecules, as indicated by the numbers in the boxes. 40% of the KIR molecules recognized one MHC molecule (black line), and 60% recognized two MHC molecules (red line). Upon infection, new KIR receptors that happened to be more cross-reactive, i.e., recognizing three MHC molecules (green line) evolved, while the most specific KIRs decreased in frequency. (B) The specificity of the KIRs in a population infected with decoy viruses. 60% of the inital KIR molecules recognized one MHC molecule (black line), 20% recognized two MHC molecules (red line), and 20% happened to recognize three different MHC molecules (green line). Over time, the frequency of those KIR molecules recognizing only one MHC molecule increased and they take over the population. (C)–(D) The average number of MHC molecules recognized per KIR molecule. In populations with highly specific KIRs ( bits), this number decreases if the individuals are infected with a virus down-regulating MHC expression (C), whereas it increases in populations infected with decoy viruses (D). (E)–(F): The average number of MHC molecules recognized per haplotype. We observed a similar behaviour as in (C)–(D). The heavy lines represent the mean number of recognized MHC molecules over ten simulations. The different colors represent the specificity values ranging from to bits. The standard deviation is depicted by the dashed lines.