Role of killer-associated protein NKG7 in NK and NKT cells

NKG7 is a poorly characterised integral membrane protein expressed on cytotoxic granules of quiescent NK and CD8 T cells and is translocated to the plasma membrane of cytotoxic cells following target engagement. It is expressed on expanded populations of cytotoxic CD4 T cells in patients with effective antiviral responses to HIV and CMV. In a transcriptional analysis of NKT cell development, we found that Nkg7is one of the most strongly up-regulated transcripts (35-fold) in NKT cells at the point of lineage commitment, suggesting it plays an important role in NKT cell activities. We have produced B6.Nkg7-/-mice and found a decrease in NK cell-mediated cytotoxicity on a per cell basis in vitro, but not an effect on numbers of peripheral NK cells. B6.Nkg7-/-mice had fewer thymic resident NK1.1+NKT cells but increased numbers in spleen and liver. The expression of the NK1.1 marker in NKT cells was associated with a “killer transcriptional program,” including strong expression of Nkg7, Gzma, Gzmb, Prf1, Fasland a wide range of NK cell markers that were not expressed on other subsets