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Nucleoside Specificity in the Carrier IgG-Dependent Induction of Tolerance¹

Department of Biochemistry and Pharmacology, Tufts University School of Medicine, Boston, Massachusetts 02111, and the Division of Immunology, The Children's Hospital Medical Center, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115

Abstract

Induction of tolerance to nucleoside haptens in BALB/c mice with isologous IgG conjugates bearing four nucleosides simultaneously (A,G,C,T)-IgG was confirmed. A mixture of separate nucleoside-IgG tolerogens (A-IgG, G-IgG, C-IgG, and T-IgG) was as effective or more effective than the (A,G,C,T)-IgG form in suppressing the response to (A,G,C,T)-KLH. The nucleosides acted independently and simultaneously, since tolerogens with varying combinations of nucleosides caused specific suppression of the respones to only those nucleosides present on the tolerogen. Nucleoside-IgG conjugates did not suppress the response to denatured DNA-methylated bovine serum albumin, in which larger oligonucleotide determinants predominate. In varying combinations, guanosine was the dominant nucleoside both for immunization and for induction of tolerance. After three or four immunizations, control immunized animals made mainly IgG anti-nucleoside antibodies and this IgG antibody formation was preferentially suppressed in tolerogen-treated animals. Tolerance could be established before the primary or secondary immunization and it then persisted for at least 75 days through a fourth course of immunization. The same dosage of tolerogen did not reverse a strongly established anti-nucleoside antibody production after a tertiary response.

Footnotes

¹ This work was supported by Grant BMS 73—06883 from the National Science Foundation (to B. David Stollar) and National Institutes of Health Grant R01-A1-11980 (to Yves Borel) and in part by the Massachusetts Lupus Erythematosus Foundation.

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