Class I (H‐2K^b) gene transfection reduces susceptibility of YAC‐1 lymphoma targets to natural killer cells

Abstract

A "hybrid gene" (MTKb) comprised of the human metallothionein IIA promoter ligated to the genomic sequence of the major histocompatibility complex class I (H-2Kb) gene was subcloned into the expression vector pSV2neo and transfected into the natural killer (NK) cell-sensitive YAC-1 lymphoma. The Kb gene product was readily detectable on the cell surface of G418-resistant transfectants using both Kb-specific monoclonal antibodies and H-2b-specific cytolytic T cells. Unlike control pSV2neo transfectants, MTKb-pSV2neo transfectants were relatively resistant to lysis by NK cells from H-2a, H-2b, H-2k or H-2 (a x b)F1 haplotype mice. These data strongly suggest that the effects of MHC expression on susceptibility to NK cells can be mediated by a single and well-defined class I molecule, Kb.

Class I-induced resistance to natural killing: identification of nonpermissive residues in HLA-A2.

“…We and others (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) have shown an inverse relationship between target-cell class I antigen expression and susceptibility to NK activity. This correlation has been verified by more direct studies in which genomic class I genes have been transfected into class I null/deficient target-cell systems (23-25, 27, 30, 39, 40).…”

“…NK cells exhibit potent MHC-unrestricted cytolytic activity against certain viral-infected and tumor target cells in vitro and in vivo (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Despite the lack of class I restriction in natural killing, the relative sensitivity of target cells to NK-mediated cytolysis may be modulated by class I antigens (14,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29).…”

Natural Killer Cell Mediated Defence Directed Selectively Against Target Cells Lacking MHC Class I Gene Products

“…The YAC-1lymphoma has also recently been transfected with H2Kb under control of the human metallothionein IIA promoter. These transfected H-2Kb positive sublines showed a reduced sensitivity to murine NK cell lysis [58].…”

Association between ICAM-1 expression and metastatic capacity of murine B-cell hybridomas

“…The protective effect against NK cell-mediated cytolysis conferred upon tumor cells by high level MHC class I antigen expression has been well documented [43]. It remains to be determined whether the upregulation of H-2K a antigen expression on B9/LPNU1L and B9/BM1 variants likewise contributes to their decreased susceptibility to NK cell activity [44]. However, the maintenance of high amounts of H-2K a antigen on B9/BM1 cells is compatible with the view that T cell surveillance mechanisms are not a significant component of host resistance to metastatic spread of B9 variants since loss of H-2K antigen expression is frequently associated with increased metastatic potential of highly immunogenic tumors [47].…”

“…A causal relationship between high level MHC class I antigen expression and resistance to NK cell-mediated cytolysis has been ascertained in other tumor systems by transfection of class I-deficient, NK cell-sensitive tumors with MHC class I genes [43]. In particular, transfection of the H-2K b gene into YAC-1 cells resulted in a marked reduction in susceptibility to NK cell activity [44]. A causative role of the H-2K d antigen in the NKresistant phenotype of metastatic B9 variants awaits similar transfection studies with B9-series cells.…”