Figure 3. Licensing results in two types of self-tolerant NK cells with respect to self-MHC.

Depicted is the situation in a mouse expressing only H2D^d which, for the sake of simplicity in this diagram, can only be recognized by Ly49A and not by Ly49C. Due to stochastic (probabilistic) [74] expression of Ly49 receptors, only cells expressing Ly49A will engage H2D^d as self-MHC, resulting in licensed NK cells. When their activation receptors are cross-linked, they readily produce cytokines. They are also capable of attacking targets lacking self-MHC and are tolerant to self because they are inhibited by self-MHC, through the same receptor (Ly49A) that conferred licensing. By contrast, NK cells not expressing Ly49A are not licensed by self-MHC, even though they express another Ly49 receptor such as Ly49C. They poorly produce cytokines when their activation receptors are cross-linked, and they are tolerant to self because they cannot be activated by targets, even those lacking self-MHC. In this context, inhibition by MHC I is not needed to achieve tolerance. To avoid clutter, activation receptors that trigger killing of susceptible targets are not shown. Adapted from [31].