Inhibition of natural killer cell cytotoxicity by cell growth-related molecules.
Certain MHC class I molecules on target cells are known to inhibit the cytotoxic action of NK cells. By using monoclonal antibody (mAb) Cho-1, we have found inhibitory non-MHC class I cell surface molecules that are noncovalently-associated with 200 kDa and 40 kDa antigens. Poly I-C-induced rat NK cells were not cytotoxic to rat fetus-derived fibroblast WFB cell line. In contrast, NK cells were cytotoxic to H-ras oncogene-induced transformants of WFB, W14 and W31. FACS analysis indicated that mAb Cho-1 reacts with WFB, but not with W14 and W31 cells. Thus, this antigen may disappear concomitantly with cell growth and transformation. Cho-1 antigens were also expressed on other NK-resistant lines, such as mouse BALB3T3 fibroblast, EL-4 lymphoma and human fibroblast HEPM. However, they were not expressed on NK-sensitive mouse YAC-1 and H-ras transformant (Brash) of BALB3T3 cells. Furthermore, treatment of target cells with IFN-gamma clearly induced the cell surface expression of Cho-1 antigens, and conferred a resistance to NK cytolysis on target cells. These data strongly suggest that Cho-1 antigen expression may correlate with target cell susceptibility to NK cells. Indeed, treatment of NK-resistant WFB as well as HEPM cells with F(ab')2 fragments of mAb Cho-1 resulted in the acquisition of susceptibility to NK cytolysis. Cho-1 antigens may be novel molecules that regulate the NK resistance of cells.
Tamura
Y
Y
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Takashima
S
S
Cho
J M
JM
Qi
W
W
Kamiguchi
K
K
Torigoe
T
T
Takahashi
S
S
Hirai
I
I
Sato
N
N
Kikuchi
K
K
D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002460:Cell Line; D002461:Cell Line, Transformed; D003602:Cytotoxicity, Immunologic; D011905:Genes, ras; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000276:immunology*; D051381:Rats; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; C092935:KIF23 protein, human; D008869:Microtubule-Associated Proteins; D007371:Interferon-gamma