title: Rat interleukin-2-activated natural killer (A-NK) cell-mediated lysis is determined by the presence of CD18 on A-NK cells and the absence of major histocompatibility complex class I on target cells.
abstract: The precise mechanism by which target cells are recognized and subsequently lysed by interleukin-2-activated natural killer (A-NK) cells is poorly understood. In this study the role of major histocompatibility complex (MHC) class I and adhesion molecules in the recognition and lysis of tumor cells was investigated in a syngeneic Wag rat model. Preincubation of tumor cells with F(ab')2 fragments of anti-MHC class I monoclonal antibody (mAb) OX18 strongly enhanced the A-NK cell-mediated lysis. Also normal syngeneic cells such as T cells and A-NK cells became highly sensitive for lysis by A-NK cells after preincubation with mAb OX18. Two other mAb against MHC class I had no effect on lysis of target cells. These data indicate that masking of MHC class I on syngeneic tumor and normal cells by mAb OX18 is sufficient for A-NK cells to recognize target cells as non-self, resulting in lysis. In addition, we found that the presence of mAb against the beta 2 (CD18)-integrins blocked the lysis of all tumor cell lines by A-NK cells in 51Cr-release assays, also when target cells were preincubated with mAb OX18. Because of the absence of CD18 on most tumor cells we concluded that a CD18-associated integrin on A-NK cells is essential for lysis of target cells. These results show that in this syngeneic rat model CD18 on A-NK cells together with MHC class I on tumor cells determine A-NK cell-mediated lysis. Furthermore, we hypothesize that the anti-MHC class I OX18 recognizes an epitope on rat MHC class I which is, or is very close to, the restriction element determining A-NK cell-mediated lysis.
authors.affiliation: Department of Pathology, University of Leiden, The Netherlands.
authors.forename: K M
authors.initials: KM
authors.lastname: Smits
authors.forename: P J
authors.initials: PJ
authors.lastname: Kuppen
authors.forename: A M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: T
authors.initials: T
authors.lastname: Tamatani
authors.forename: M
authors.initials: M
authors.lastname: Miyasaka
authors.forename: G J
authors.initials: GJ
authors.lastname: Fleuren
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D000954:Antigens, Surface / Q000502:physiology; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules / Q000502:physiology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I