Synthetic macrophages: liposomes bearing antigen, class II MHC and membrane-IL-1.
Liposomes containing membrane-IL-1, Iak, and the antigen conalbumin were evaluated as "synthetic macrophages." The role of these three molecules in macrophage-T cell interaction was studied by testing the ability of such synthetic macrophages to induce the proliferation of a T cell clone specific to conalbumin (the D10 cell line) or immune spleen cells sensitized three times in vivo with conalbumin. In the latter case, splenic macrophages were eliminated by adherence and a lysomotropic agent. The antigen conalbumin was presented on the surface of the liposomes in two forms: as native undigested protein or as a complex of Iak and naturally processed peptides isolated from peritoneal macrophages incubated with conalbumin. When the liposomes presented the Ia antigen associated with conalbumin-peptides and membrane-IL-1, the proliferation of both the D10 and the immune spleen cells was high and maximal. The proliferation response of both cell types was completely dependent on the presence of membrane-IL-1, since no proliferation occurred when liposomes were prepared with only conalbumin-peptides bound to Iak. Therefore, it could be concluded that processed antigen associated with class II MHC antigen and membrane-IL-1 were required for T cell activation. When the liposomes presented native conalbumin, Iak, and membrane-IL-1, significant proliferation occurred, but if the liposomes lacked membrane-IL-1, the proliferation of the T cell clone and the spleen cells decreased to only 40-50% of the previous signal. In this case native conalbumin and class II antigen alone were required for T cell activation, while membrane-IL-1 alone amplified the response. When the liposomes were made with only Iak and membrane-IL-1, lacking either form of conalbumin, there was no proliferation of antigen-specific target cells. These results indicated that in this synthetic system, membrane-IL-1 is essential for the proliferative response of antigen-specific T cells when conalbumin is presented as processed peptides in association with Iak.
Department of Cell Biology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
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Bakouche
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Lachman
D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D003207:Conalbumin / Q000276:immunology; D004337:Drug Carriers; D000949:Histocompatibility Antigens Class II / Q000008:administration & dosage*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000008:administration & dosage*; D007700:Kinetics; D008081:Liposomes; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D004337:Drug Carriers; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D008081:Liposomes; D003207:Conalbumin