A novel technique to link either proteins or peptides to gammaglobulin to construct tolerogens.
In order to extend the concept of constructing tolerogens (i.e., compounds which induce immunologic tolerance), we developed a novel method to covalently link either protein or peptide to isologous gammaglobulin. We used disuccinimidyl suberate (DSS) for preparing protein conjugates in solution in a novel use of this reagent. We tested the efficacy of this method in two different experimental models: in the first, we found that administration of pigeon cytochrome C conjugated to mouse IgG in vivo induces T cell unresponsiveness in vitro. In the second, we induced unresponsiveness to factor VIII light chain both in newborn and, more importantly, in adult mice already immune to factor VIII. We hope that this simple method will provide a powerful tool to construct tolerogens useful in the specific treatment of either allergic or autoimmune diseases.
Borel
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Center for Blood Research, Harvard Medical School, Boston, MA 02115.
Borel
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Y
D000818:Animals; D002850:Chromatography, Gel; D010856:Columbidae; D003432:Cross-Linking Reagents; D003574:Cytochrome c Group / Q000378:metabolism* / Q000494:pharmacology; D005169:Factor VIII / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000378:metabolism*; D007158:Immunologic Techniques; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011058:Pollen / Q000378:metabolism; D013388:Succinimides; D013601:T-Lymphocytes / Q000276:immunology
D003432:Cross-Linking Reagents; D003574:Cytochrome c Group; D007074:Immunoglobulin G; D013388:Succinimides; D005169:Factor VIII; C019358:disuccinimidyl suberate