Table 2.
NKp44 splice variants
| Article | Model/targets | Conditions/effectors | Results | |
|---|---|---|---|---|
| Campbell et al. (J. Immunol. 2004) [22] | Chimeric KIR3DL1/KIR2DL4 fusion protein. Redirected P815 target cell lysis model using anti KIR3DL1 mAb | 3DL1.p44.wt chimeric receptor, NK-92 cells | No inhibition. Tyrosine phosphorylation of NKp44 ITIM. No SHP-1, SHP-2, SHIP recruitment or binding. No AP-2 clathrin adaptor μ2 association | |
| Rosental, Brusilovsky, and Hadad et al. (J. Immunol. 2011) [38] | PCNA overexpression in HeLa cells | IL-2 stimulated human primary NK cells | Reduced IFNγ secretion and lysis | |
| NKL | No effect on IFNγ secretion and lysis | |||
| PCNA overexpression in HeLa cells or PCNA siRNA in HeLa, PCNA-1, MCF7, Du145, U251, and A375 cell lines | NK-92 | No effect on IFNγ secretion and lysis | ||
| NK-92-NKp44(ITIM+) | Reduced IFNγ secretion and lysis relative to NK-92 cells | |||
| PCNA overexpression in HeLa cells | NK92-44Δ204E (ITIM deletion) | No effect on IFNγ secretion, lysis and CD107a degranulation relative to NK-92 cells | ||
| NK92-44Y238F (ITIM mutation) | No effect on IFNγ secretion, lysis and CD107a degranulation relative to NK-92 cells | |||
| Horton et al. (PloS One 2013) [39] | Membranal PCNA/HLA-I complex on DB cells | NK-92MI | mAb blocking of NKp44 increased lysis of target cells | |
| IL-2 stimulated human primary NK cells | mAb blocking of NKp44 increased lysis of target cells | |||
| Siewiera et al. (Nature communications 2015) [34] | mAb ligation of NKp44, mAbs co-ligation of NKp44 and NKp46, qPCR using SYBR green | Fresh isolated Human decidual NK cells | Similar levels of NKp44-1/NKp44-2/NKp44-3. NKp44 ligation had no effect on CD107a with low immune synapse formation. NKp44 and NKp46 co-ligation reduced CD107a | |
| IL-15; overnight stimulation, isolated human primary NK cells | Higher level of NKp44-2 relative to NKp44-1 and NKp44-3. NKp44 ligation Increase in CD107a, high immune synapse formation. NKp44 and NKp46 co-ligation had incremental effect on CD107a | |||
| Cytokine stimulation of isolated human primary NK cells for 6 days. NKp44 splice variant analysis by qPCR using SYBR green. Expression of NKp44 splice variants relative to pNK cells cultured in cytokine free medium with or without lysis of P815 target cells or cytokine secretion after mAb ligation of NKp44 | IL-15 | Increased expression of NKp44-1 and NKp44-3 | ||
| IL-18 | Increased expression of NKp44-2 and NKp44-3 | |||
| IL-15/IL-18 | Increased expression of NKp44-1 and NKp44-3, increased lysis, increased secretion of TNFα/IFNγ/CCL3/VEGF-A | |||
| TGFβ | Increased expression of NKp44-1, No effect on lysis or on the secretion of TNFα/IFNγ/CCL3/VEGF-A | |||
| TGFβ/IL-15 | Increased expression of NKp44-1 and NKp44-3 | |||
| TGFβ/IL-18 | Increased expression of NKp44-3 | |||
| TGFβ/IL-15/IL-18 | Increased expression of NKp44-1 and NKp44-3, increased lysis, increased secretion of TNFα/IFNγ/CCL3/VEGF-A | |||
| Shemesh, Brusilovsky et al. (Oncotarget 2016) [13] | Human PBMC. Analysis of NKp44 protein by flow-cytometry and NKp44 splice variants by qPCR using TaqMan | Fresh | No NKp44 protein expression. Basal NKp44 mRNA levels; similar levels of NKp44-1, NKp44-2 and NKp44-3 | |
| IL-2 or IL-15 stimulation for 6 days | NKp44 protein expression on NK/ NKT cells. Increased NKp44 mRNA; Higher levels of NKp44-1 and NKp44-3 relative to NKp44-2 | |||
| Isolated human primary NK cells/ analysis of NKp44 protein by flow-cytometry and NKp44 splice variants by qPCR using TaqMan. Lysis assay against PCNA-overexpressing HeLa cells and THP1 with or without mAb blocking of NKp44 | Fresh | No protein expression. Basal NKp44 mRNA; similar levels of NKp44-1, NKp44-2, and NKp44-3. No lysis | ||
| IL-2 or IL-15 stimulation for 6 days | NKp44 protein expression on NK cells. Increase NKp44 mRNA; Higher level of NKp44-1 and NKp44-3 relative to NKp44-2. NKp44-1 > 66% of NKp44 mRNA. Reduced lysis of PCNA-overexpressing HeLa cells. Blocking NKp44 increased the lysis of HeLa and THP1 cells | |||
| Human NK cell lines with or without NKp44 splice variant overexpression. NKp44 splice variant analysis by qPCR using TaqMan. IFNγ secretion, lysis, and immune synapse formation using a PCNA-overexpressing HeLa cell model | KHYG1 or NK-92 | NKp44-1 and NKp44-3 are co-dominantly expressed. No reduction in lysis of IFNγ secretion | ||
| NK-92-NKp44-1, NK-92-NKp44-2, NK-92-NKp44-3 | NKp44-1 overexpression but not NKp44-2 or NKp44-3, reduced lysis, IFNγ secretion, and immune synapse formation | |||
| RNAseq data of acute myeloid leukemia patients. (TCGA). PBMC samples. Survival of newly diagnosed patients | Solitary profile of NKp44-1 vs. mix profile of NKp44 splice variants vs. NKp44 negative samples | Solitary expression of NKp44-1 was significantly associated with poor survival of newly diagnosed AML patients | ||
| Shemesh et al. (Oncotarget 2016) [37] | qPCR analysis of NKp44 splice variants using TaqMan | First trimester placental tissue; Elective vs. Spontaneous abortions | Elective abortions; NKp44-1 expression > 66% of NKp44 mRNA in 80% of the cases. Spontaneous abortions; NKp44-1 expression < 66% of NKp44 mRNA in 80% of the cases | |
| Third trimester placental tissue; Term labor vs. Preeclampsia labor | Term labors; NKp44-1 expression > 66% of NKp44 mRNA in 80% of the cases. Preeclampsia labor; NKp44-1 expression > 66% of NKp44 mRNA in 50% of the cases | |||
| Lung cancer tissue; Tumor vs. matched Normal | Higher incidence of NKp44 mRNA in the tumor tissue. NKp44-1 expression > 66% of NKp44 mRNA in 80% of the cases | |||
| RNAseq data of Breast, Lung, Cervical/Uterine, Kidney, Gastrointestinal tract organs, Gastrointestinal (GI) tract accessory organs solid tumors (TCGA) | Solid tumor samples vs. matched normal tissue | Higher incidence of NKp44 mRNA in Breast, Lung and Cervical/Uterine tumor tissue. NKp44-1 expression > 66% of NKp44 mRNA in 80% of all the cases | ||