SUPPRESSION OF REAGINIC ANTIBODY-FORMATION .3. RELATIONSHIP BETWEEN IMMUNOGENICITY AND TOLEROGENICITY OF HAPTEN-CARRIER CONJUGATES

  • 1 January 1976
    • journal article
    • research article
    • Vol. 116  (6) , 1711-1718
Abstract
From the study of the effect of epitope density on the immunogenicity of haptenated ovalbumin (DNP[dinitrophenylated]-OA) it was concluded that the lightly haptenated conjugate, DNP0.5-OA, induced only low titers of anti-DNP hemagglutinating [mouse] antibody, no reaginic antibodies to the hapten and high reaginic and high hemagglutinating antibody responses to the carrier. The conjugate with a slightly higher degree of haptenation, i.e., DNP2.3-OA, induced reaginic and hemagglutinating antibodies to the hapten and the carrier. The heavily haptenated conjugate, DNP20-OA, elicited reaginic and hemagglutinating antibodies only against the hapten but not against the carrier. Specific suppression of anti-hapten reaginic antibody formation was achieved by treatment of mice with a tolerogen consisting of the hapten (DNP) conjugated covalently to isologous [mouse] .gamma. globulins (M.gamma.G). The epitope density of the DNPx-M.gamma.G conjugates played a dominant role in determining whether or not the conjugate was tolerogenic. Lightly haptenated conjugates (DNP0.5-M.gamma.G, DNP1.3-M.gamma.G or DNP1.9-M.gamma.G) were not tolerogenic, moderately haptenated conjugates (DNP4.2-M.gamma.G, DNP8-M.gamma.G, and DNP14-M.gamma.G) were tolerogenic, and heavily haptenated conjugates (DNP32-M.gamma.G and DNP53-M.gamma.G) were immunogenic, being capable of priming the recipients for the DNP hapten. Further evidence for the nonimmunogenicity of DNP8-M.gamma.G conjugate was inferred from its rate of clearance in tolerized and normal mice. The 1/2-life of 125I-labeled DNP8-M.gamma.G in circulation was not significantly different for normal and tolerized mice; it was 3.7 and 3.5 days, respectively, which is within the range of data reported for clearance of normal M.gamma.G. DNP8-M.gamma.G was apparently catabolized at a rate similar to that of nonconjugated, isologous M.gamma.G. There was no significant difference in the localization of DNP8-M.gamma.G in identical organs (spleen, thymus, kidney and liver) of normal and tolerized mice. All the multivalent DNPx-M.gamma.G conjugates were able to elicit passive cutaneous anaphylaxis (PCA) reactions on i.v. challenge of rats which were pre-sensitized i.d. intradermally with anti-DNP reaginic antibodies.