Effect of lipid A incorporation on characterization of liposomal model membranes as thymus-independent type 1 or type 2 immunogens.
We used the following criteria to determine whether liposomal model membranes are thymus-independent type 1 (TI-1) or type 2 (TI-2) immunogens: a) in vivo response of (CBA/N X BALB/c)F1 male and female mice; b) in vitro response of spleen cells from these mice; c) ontogeny of the response in cultures of (C57BL/6 X DBA/2)F1 male cells obtained from mice of different ages; d) ability of a monoclonal anti-delta antibody to block the in vitro response of C57BL/6 spleen cells. The liposomes were sensitized with N(2,4,6-trinitrophenyl-6-N-aminocaproyl)-dipalmitoylphosphatidylethanolamine (TNP-Cap-DPPE) and were prepared without and with incorporation of the B cell mitogen, lipid A. On the basis of the above criteria, liposomes prepared without lipid A can be characterized as a TI-2 immunogen and resemble TNP-Ficoll. In contrast, liposomes prepared with lipid A behave like a TI-1 immunogen such as TNP-BA (trinitrophenylated Brucella abortus). Conversion of liposomes from a TI-2 to a TI-1 immunogen by inclusion of lipid A in the bilayers was achieved under conditions of constant TNP-Cap-DPPE epitope density. Increasing the epitope density in liposomes made without lipid A does not result in transformation of immunogen type. These results, which bear on the features that may distinguish TI-1 from TI-2 immunogens, are discussed with regard to the involvement of macrophages and T cells in the response.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D000921:Antibody-Producing Cells / Q000276:immunology; D005260:Female; D007072:Immunoglobulin D / Q000276:immunology; D008050:Lipid A / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008081:Liposomes / Q000276:immunology; D008297:Male; D008567:Membranes, Artificial; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D010714:Phosphatidylethanolamines / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D007072:Immunoglobulin D; D008050:Lipid A; D008070:Lipopolysaccharides; D008081:Liposomes; D008567:Membranes, Artificial; D010714:Phosphatidylethanolamines; C033368:N-(2,4,6-trinitrophenyl-6-N-aminocaproyl)-1,2-dipalmitoylphosphatidylethanolamine