MHC class-I antigen deficiency, malignancy and susceptibility of P815 mastocytoma to NK and macrophage killing.
A subline of the murine P815 mastocytoma passaged for a long period of time in histoincompatible hosts was found to be deficient in surface MHC class-I antigens by serological and biochemical methods. In agreement with the lack of restriction elements, this variant cell line was no longer susceptible to killing by cytotoxic T cells stimulated by and directed against the parental tumor cell line in syngeneic DBA-2 hosts. We did not observe the appearance of susceptibility to NK killing concomitantly with H-2 loss. We thus could not confirm the hypothesis of a regulatory function of H-2 structures in NK recognition/killing. Both cell lines were also resistant to lysis by mouse macrophages. The parental cell line was sensitive to rat macrophage killing, whereas the variant line had lost such sensitivity. In spite of resistance in vitro to various defense mechanisms, the variant H-2 loss tumor cell line was less tumorigenic in syngeneic hosts and exhibited a lower metastatic capacity than the parental cell line. We propose that in the H-2 loss subline, survival of cells in vivo is impeded since positive signals mediated by H-2 structures are missing, which are necessary for cell-cell contact and survival.
Bertschmann
M
M
Theodor Kocher Institute, University of Bern, Switzerland.
Käsermann
D
D
Keller
R
R
D000818:Animals; D002470:Cell Survival / Q000276:immunology; D003165:Complement System Proteins / Q000502:physiology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000172:deficiency* / Q000502:physiology; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D012515:Mast-Cell Sarcoma / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D011233:Precipitin Tests
D015395:Histocompatibility Antigens Class I; D003165:Complement System Proteins