Jc. Ryan et al., NKR-P1A IS A TARGET-SPECIFIC RECEPTOR THAT ACTIVATES NATURAL-KILLER-CELL CYTOTOXICITY, The Journal of experimental medicine, 181(5), 1995, pp. 1911-1915
NKR-P1A is a lectinlike surface molecule expressed on rat natural kill
er (NK) cells. NKR-P1A has structural and functional features of an ac
tivating NK cell receptor, but a requirement for NKR-P1A in target cel
l lysis has not been determined. To define the role of NKR-P1A in natu
ral killing, we have generated a mutant of the rat NK cell line, RNK-1
6, lacking expression of all members of the NKR-P1 receptor family. Al
though these NKR-P1-deficient NK cells were able to kill many standard
tumor targets, including YAC-1, they were selectively deficient in th
e lysis of IC-21 macrophage, B-16 melanoma, and C1498 lymphoma targets
. Reexpression of a single member of the NKR-P1 family, NKR-P1A, on mu
tant cells restored lysis of IC-21, and killing of IC-21 targets throu
gh rat NKR-P1A was completely blocked by F(ab')(2) anti-NKR-P1A. Reexp
ression of NKR-P1A also restored transmembrane signaling to IC-21, as
assessed by the generation of inositol-1,4,5-trisphosphate. The genera
tion of inositol-1,4,5-trisphosphate was also restored in response to
B-16 targets, but both B-16 and C1498 cells remained resistant to lysi
s, indicating that other NK cell molecules, perhaps within the NKR-P1
family, are required for the efficient killing of these tumors. These
results are the first to demonstrate that NKR-P1A is a target-specific
receptor that activates natural killing.