Killer activation receptor

They can have a tyrosine containing activation or inhibitory motifs in the intracellular part of the receptor molecule (they are called ITAMs and ITIMs).

At first, it was thought that there was only one KAR and one KIR receptor present on the NK cell, known as the two-receptor model.

[5]Even though KARs and KIRs are receptors with antagonistic effects on NK cells, they have some structural characteristics in common.

Also, the extracellular domains of these proteins tend to have similar molecular features and are responsible for ligand recognition.

KARs proteins possess positively charged transmembrane residues and short cytoplasmic tails that contain few intracellular signaling domains.

As the chains from KARs are not able to mediate any signal transduction in isolation, a common feature of such receptors is the presence of noncovalently linked subunits that contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic tails.

These subunits are moreover composed of an accessory signaling molecule such as CD3ζ, the γc chain, or one of two adaptor proteins called DAP10 and DAP12.

[6] A common feature of members of all KIR is the presence of immunoreceptor tyrosine-based inhibition motifs (ITIMs) in their cytoplasmic tails.

This is how ITIMs counteract the effect of kinases initiated by activating receptors and manage to inhibit the signal transduction within the NK cell.

The two other classes are: Natural Killer Group 2 (NKG2), which includes activation and inhibition receptors, and some KIRs which do not have an inhibitor role.

Finally, there is CD16, a low affinity Fc receptor (FcγRIII) which contains N-glycosylation sites; therefore, it is a glycoprotein.

In fact, these intracellular domains determine the opposite functions of activation and inhibitory receptors.

NK can kill directly the hosted cell, it can do it by segregating cytokines, IFN-β and IFN-α, or by doing both things.

[9] Then, Killer Inhibitory Receptors (KIRs) examine the surface of the tumor cell in order to determine the levels of MHC class I molecules it has.

However, if KIRs are not sufficiently engaged to MHC class I molecules, killing of the target cell proceeds.

When a KAR binds to MICA and MICB molecules on the surface of an infected cell (or a tumor cell), a KIR examines the levels of MHC class I of this target cell. If the MHC class I levels are enough, killing of the cell doesn't proceed (left), but if they aren't, the killing signal proceeds and the cell is eliminated (right).
When the ligand binds to the KAR, ITAMs in cytoplasmic tail of the receptor are phosphorylated by the kinase PTK and the transduction signal takes place. The accessory signaling molecule CD3ζ and the adaptor protein DAP10 or DAP12 have been simplified for a better comprehension.