NK cells kill any cells devoid of reduced MHC I molecules on their surface. MHC I molecule is expressed by all nucleated cells except RBCs, sperm cells and others. So how can non-nucleated cells like RBCs escape NK cell killing?
While MHC I are the classic inhibitory signal for NK cell killing, there are a number of other ones, as well as activating ligands for NK cell killing that are not present on the surface of RBCs. It is the balance of inhibitory and activating signals that determines the NK cell activity
RBCs express CD47. The presence of CD47 molecule allows RBCs to be recognised as self by NK cells through ligation of SIRP1alpha. This signalling provides an inhibitory signal to NK cells.
Dear Hylemariam Mihiretie,
Why do you think, that erythrocytes are not carriers of HLA molecules on their surface?
Leastwise reticulocytes and young erythrocytes are carrier of HLA class I molecules!
This HLA class I molecules on erythrocytes are well known, called Bennett-Goodspeed (Bg) blood groups: Bga = HLA-B7, Bgb = HLA-B17, Bgc = HLA-A28.
(B17 = B57 & B58 and A28 = A68 & A69)
On the other hand young and old erythrocytes are able to catch (adsorb) soluble HLA molecules from the blood plasma.
Best regards,
Thomas
I do totally agree with Thomas. Adsorbing soluble antigens on the Surface of the RBCs is a common feature of erythrocytes (e.g., Lewis). However, one could think how could the in vitro generated HLA-deficient platelets escape the NK cells attack? Interesting!
The answer to your question may lie in the mode of activation of NK cells. NK cells have a two-part trigger: a suppressor and an activator. The suppressor prevents the cell from being activated, while the activator activates the cell to work on a target and destroys the target.
In order for an NK cell to destroy an RBC, both specific activators (ligands) and suppressors (MHC class 1) must be present on the RBC surface. However, since RBCs lack these molecules, they are not recognized as targets by NK cells and are thus spared from destruction.
It's also possible that RBCs further protect themselves by expressing CD47, which is a major recognition molecule of NK cells, or by not having a signal that would fall into the category of DAMP (damage-associated molecular pattern). However, these factors do not change the important point about NK's mode of activation - namely that without specific activators and suppressors present on their surface, RBCs are safe from destruction by NK cells.
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