Surrogate receptor-mediated cellular cytotoxicity. A method for "custom designing" killer cells of desired target specificity.
Palmitate-derivatized antibody molecules can function as surrogate receptors when incorporated into the plasma membranes of nylon wool non-adherent spleen cells. Surrogate receptor molecules are attached to the membranes by insertion of the palmitate hydrocarbon chains into the phospholipid bilayer. This mode of attachment precludes interactions between surrogate receptors and intracellular and intramembranous structures. Despite these limitations, surrogate receptors consisting of either palmitate-derivatized intact antibody molecules or their corresponding F(ab')2 fragments specific for Ag on syngeneic B lymphocytes or hapten-modified EL-4 lymphoma cells can direct cell-mediated cytotoxic activity against the appropriate target. Treatment of the surrogate receptor-decorated effector cell populations with anti-asialo GM1 plus C eliminated the observed target cell lysis, suggesting a role for NK cells in this cytolytic process. The efficiency of this surrogate receptor-mediated cellular cytotoxicity parallels that of natural receptor-mediated target cell lysis and is not limited by inherent resistance of a target cell to NK cell-mediated cytotoxicity. Application of this technology to study the requirements for productive lytic interactions between effector and target cells may provide valuable insights into the mechanism of cell-mediated cytotoxicity. Furthermore, these results provide the rationale for future studies designed to evaluate the ability of surrogate receptors to focus cytotoxic cell activity onto a specified target in situ, in an attempted elimination of diseased cells.
Colsky
A S
AS
Department of Microbiology, University of Miami School of Medicine, FL 33101.
Stein-Streilein
J
J
Peacock
J S
JS
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D019308:Palmitic Acid; D010169:Palmitic Acids; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011971:Receptors, Immunologic; D013154:Spleen / Q000166:cytology; D014407:Tumor Cells, Cultured / Q000276:immunology
D007140:Immunoglobulin Fab Fragments; D010169:Palmitic Acids; D011947:Receptors, Antigen, B-Cell; D011971:Receptors, Immunologic; D019308:Palmitic Acid