NUCLEOSIDE SPECIFICITY IN CARRIER IGG-DEPENDENT INDUCTION OF TOLERANCE

Abstract

Induction of tolerance to nucleoside haptens in BALB/c mice with isologous IgG [immunoglobulin G] conjugates bearing 4 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 [keyhole limpet hemocyanin]. The nucleosides acted independently and simultaneously, since tolerogens with varying combinations of nucleosides caused specific suppression of the response 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 for immunization and for induction of tolerance. After 3 or 4 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 4th course of immunization. The same dosage of tolerogen did not reverse a strongly established anti-nucleoside antibody production after a tertiary response.