Briefly about KIR proteins

KIR family of the immunoglobulin-like receptors is constituted by a group of CD158 isoforms (see table below), which are expressed on NK and Tc cells, usually 2-6 different isoforms on each cell. KIR proteins can contain either two extracellular domains (KIR2D--) or three extracellular domains (KIR3D--) and can have either short intracellular domain (-----S-) or long intracellular domain (-----L-). Those with long intracellular domain have inhibitory effect on NK and T cell cytotoxicity, whereas those with short intracellular domain have activating function. The last number in their code name represents the number of a member of the particular KIR subfamily. For example CD158e1 (KIR3DL1), CD158k (KIR3DL2), and CD158z (KIR3DL3) are all the inhibitory receptors with three extracellular Ig-like domains, similarly CD158a (KIR2DL1), CD158b (KIR2DL2/KIR2DL3), CD158d (KIR2DL4), and CD158f (KIR2DL5) are the inhibitory receptors with two extracellular domains. CD158 molecules with activating functions have mostly two extracellular domains, such as CD158h (KIR2DS1), CD158j (KIR2DS2), KIR2DS3, CD158i (KIR2DS4), and CD158g (KIR2DS5), but CD158e2 (KIR3DS1) has three. CD158c does not have fully elucidated structure, hence we do not include it in this list.


KIR family proteins

KIR2DS3 (no CD code yet) - activating

CD158a (KIR2DL1) - inhibitory

CD158b (KIR2DL2/KIR2DL3) - inhibitory

CD158d (KIR2DL4) - inhibitory

CD158e1 (KIR3DL1) - inhibitory

CD158e2 (KIR3DS1) - activating

CD158f (KIR2DL5) - inhibitory

CD158g (KIR2DS5) - activating

CD158h (KIR2DS1) - activating

CD158i (KIR2DS4) - activating

CD158j (KIR2DS2) - activating

CD158k (KIR3DL2) - inhibitory

CD158z (KIR3DL3) - inhibitory


Fig. 1: Schematic drawing of KIR family proteins.

Due to their important roles in maintaining the ballance between self tolerance and cytotoxic mechanisms of the immune system, KIR proteins are being intensively studied. Recently e.g. the CD158z protein (KIR3DL3) has become a very attractive target for immunotherapy. Interaction of CD158z with its receptor HHLA2 (B7H7, B7H5) protects HHLA2-expressing cells against cytotoxic mechanisms. As HHLA2 is frequently expressed in various cancers, it provides them an immune evasion mechanism independent from PD1-PDL1 pathway. However, because CD158z, like other KIR proteins, is highly polymorphic in the population, there remains a lot of work to be done on this topic.
Available antibodies in EXBIO portfolio:
mAb#33: Detects inhibitory isoform KIR2DL4 (CD158d).
Formats: purified (11-609-C100), low endotoxin (12-609-C100), PE (1P-609-T100), APC (1A-609-T100), Alexa Fluor® 647 (A6-609-T100), PE-Cy™5 (T8-609-T100), PE-Cy™7 (T7-609-T100)
UP-R1: Detects inhibitory isoform KIR2DL5 (CD158f).
Formats: purified (11-774-C100), PE (1P-774-T100), APC (1A-774-T100)
CH21: Detects inhibitory isoform KIR3DL3 (CD158z).
Formats: purified (11-945-C100), PE (1P-945-C100), APC (1A-945-C100)
HP-MA4: Detects activating isoforms KIR2DS1 (CD158h), KIR2DS3, KIR2DS5 (CD158g), and the inhibitory isoform KIR2DL1 (CD158a).
Formats: purified (11-775-C100), PE (1P-775-T100), PE-Cy™7 (coming soon)

Fig. 2: Verification of CH21 antibody specificity regarding KIR3DL3 (CD158z). Tested by flow cytometry on HEK-293 cells transfected with KIR2DL5A, KIR3DL1, KIR3DL2, and KIR3DL3 coding plasmids co-transfected with YFP coding plasmid; non-transfected HEK-293 cells used as the negative control. APC conjugated CH21 antibody used in the concentration 10 μg/ml.


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