NK sensitivity, H-2 expression and metastatic potential: analysis of H-2Dk gene transfected fibrosarcoma cells.
We have used the 3-Methylcholanthrene induced T-10 fibrosarcoma tumour cell system (H-2b xH-2k)F1 to elucidate the possible correlation between metastatic potential, expression of individual H-2 antigens and susceptibility to NK cells. Transfection of the non-metastatic and NK sensitive IC9 cells (Db+, Dk-, Kb-, Kk-) with the H-2Dk gene, altered the metastatic phenotype of the parental cells, yet had no effect on the susceptibility of these tumour cells to lysis by NK and did not elicit a specific CTL response in syngeneic hosts. Variants of the metastatic and NK resistant IE7 clone (Db+, Dk+, Kb-, Kk-), lacking H-2Dk, were selected by treatment with monoclonal anti H-2Dk antibodies and complement. These variants were sensitive to NK and poorly or non metastatic. Retransfection of 'Dk' 'loss' variants with the H-2Dk gene, resulted in the isolation of several clones expressing a wide range of metastatic phenotypes but maintained sensitivity to NK. These results indicate that the H-2D region of the MHC and or closely linked genes may be involved in the complex interrelationship between target susceptibility to NK and metastasis.
Gopas
J
J
Department of Microbiology & Immunology, Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel.
Rager-Zisman
B
B
Har-Vardi
I
I
Hammerling
G J
GJ
Bar-Eli
M
M
Segal
S
S
D000818:Animals; D000911:Antibodies, Monoclonal; D003165:Complement System Proteins; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005354:Fibrosarcoma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000556:secondary; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D007694:Killer Cells, Natural / Q000276:immunology*; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D014162:Transfection
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D008748:Methylcholanthrene; D003165:Complement System Proteins