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INDUCTION OF IMMUNITY AND TOLERANCE IN VITRO BY HAPTEN PROTEIN CONJUGATES : I. THE RELATIONSHIP BETWEEN THE DEGREE OF HAPTEN CONJUGATION AND THE IMMUNOGENICITY OF DINITROPHENYLATED POLYMERIZED FLAGELLIN

Of many dinitrophenylated (DNP) protein conjugates tested, only DNP conjugated to polymerized flagellin (DNP-POL) (or the structurally related bacterial flagella) elicited a primary anti-DNP response in vitro. Other DNP proteins, such as DNP-monomeric flagellin (DNP-MON), were capable of inducing se...

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Autor principal: Feldmann, Marc
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1972
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2139147/
https://www.ncbi.nlm.nih.gov/pubmed/5062922
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author Feldmann, Marc
author_facet Feldmann, Marc
author_sort Feldmann, Marc
collection PubMed
description Of many dinitrophenylated (DNP) protein conjugates tested, only DNP conjugated to polymerized flagellin (DNP-POL) (or the structurally related bacterial flagella) elicited a primary anti-DNP response in vitro. Other DNP proteins, such as DNP-monomeric flagellin (DNP-MON), were capable of inducing secondary responses in vitro. The capacity of DNP-POL to immunize spleen cell suspensions devoid of thymus-derived cells was the reason for the greater immunogenicity of DNP-POL, since even large numbers of flagellin-reactive activated thymus cells did not increase the anti-DNP response of normal spleen cells immunized with DNP-POL, whereas the thymus-dependent response to DNP-MON was markedly increased. The capacity of various batches of DNP-POL to immunize normal spleen cells in vitro varied markedly, depending on the number of DNP groups conjugated. DNP-POL with few DNP groups conjugated was immunogenic, but even at very high concentrations did not induce tolerance. In contrast, highly conjugated DNP-POL did not immunize, but readily induced tolerance. DNP-POL with intermediate degrees of conjugation were, like unconjugated polymeric flagellin, capable of inducing both immunity and tolerance. Since DNP-POL immunizes bone marrow-derived lymphocytes (B cells) directly the reduced response was not due to a masking of carrier determinants, necessary for cell collaboration. By using mixed DNP-5-(dimethylamino)-1-naphthalyl (dansyl)-POL conjugates, it was found that the inhibitory effect of a high degree of hapten conjugated was hapten specific. Depolymerization of DNP-POL to DNP-MON, which does not induce primary anti-DNP responses, was excluded by centrifugation analysis and electron microscopy. The relationship of the degree of hapten conjugation on DNP-POL to the capacity to induce tolerance and immunity in B cells has clarified the mechanism of immunological triggering of these cells. A model of the mechanism of "signal" discrimination between immunity and tolerance in B cells, based on these findings, is proposed.
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spelling pubmed-21391472008-04-17 INDUCTION OF IMMUNITY AND TOLERANCE IN VITRO BY HAPTEN PROTEIN CONJUGATES : I. THE RELATIONSHIP BETWEEN THE DEGREE OF HAPTEN CONJUGATION AND THE IMMUNOGENICITY OF DINITROPHENYLATED POLYMERIZED FLAGELLIN Feldmann, Marc J Exp Med Article Of many dinitrophenylated (DNP) protein conjugates tested, only DNP conjugated to polymerized flagellin (DNP-POL) (or the structurally related bacterial flagella) elicited a primary anti-DNP response in vitro. Other DNP proteins, such as DNP-monomeric flagellin (DNP-MON), were capable of inducing secondary responses in vitro. The capacity of DNP-POL to immunize spleen cell suspensions devoid of thymus-derived cells was the reason for the greater immunogenicity of DNP-POL, since even large numbers of flagellin-reactive activated thymus cells did not increase the anti-DNP response of normal spleen cells immunized with DNP-POL, whereas the thymus-dependent response to DNP-MON was markedly increased. The capacity of various batches of DNP-POL to immunize normal spleen cells in vitro varied markedly, depending on the number of DNP groups conjugated. DNP-POL with few DNP groups conjugated was immunogenic, but even at very high concentrations did not induce tolerance. In contrast, highly conjugated DNP-POL did not immunize, but readily induced tolerance. DNP-POL with intermediate degrees of conjugation were, like unconjugated polymeric flagellin, capable of inducing both immunity and tolerance. Since DNP-POL immunizes bone marrow-derived lymphocytes (B cells) directly the reduced response was not due to a masking of carrier determinants, necessary for cell collaboration. By using mixed DNP-5-(dimethylamino)-1-naphthalyl (dansyl)-POL conjugates, it was found that the inhibitory effect of a high degree of hapten conjugated was hapten specific. Depolymerization of DNP-POL to DNP-MON, which does not induce primary anti-DNP responses, was excluded by centrifugation analysis and electron microscopy. The relationship of the degree of hapten conjugation on DNP-POL to the capacity to induce tolerance and immunity in B cells has clarified the mechanism of immunological triggering of these cells. A model of the mechanism of "signal" discrimination between immunity and tolerance in B cells, based on these findings, is proposed. The Rockefeller University Press 1972-03-31 /pmc/articles/PMC2139147/ /pubmed/5062922 Text en Copyright © 1972 by The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Feldmann, Marc
INDUCTION OF IMMUNITY AND TOLERANCE IN VITRO BY HAPTEN PROTEIN CONJUGATES : I. THE RELATIONSHIP BETWEEN THE DEGREE OF HAPTEN CONJUGATION AND THE IMMUNOGENICITY OF DINITROPHENYLATED POLYMERIZED FLAGELLIN
title INDUCTION OF IMMUNITY AND TOLERANCE IN VITRO BY HAPTEN PROTEIN CONJUGATES : I. THE RELATIONSHIP BETWEEN THE DEGREE OF HAPTEN CONJUGATION AND THE IMMUNOGENICITY OF DINITROPHENYLATED POLYMERIZED FLAGELLIN
title_full INDUCTION OF IMMUNITY AND TOLERANCE IN VITRO BY HAPTEN PROTEIN CONJUGATES : I. THE RELATIONSHIP BETWEEN THE DEGREE OF HAPTEN CONJUGATION AND THE IMMUNOGENICITY OF DINITROPHENYLATED POLYMERIZED FLAGELLIN
title_fullStr INDUCTION OF IMMUNITY AND TOLERANCE IN VITRO BY HAPTEN PROTEIN CONJUGATES : I. THE RELATIONSHIP BETWEEN THE DEGREE OF HAPTEN CONJUGATION AND THE IMMUNOGENICITY OF DINITROPHENYLATED POLYMERIZED FLAGELLIN
title_full_unstemmed INDUCTION OF IMMUNITY AND TOLERANCE IN VITRO BY HAPTEN PROTEIN CONJUGATES : I. THE RELATIONSHIP BETWEEN THE DEGREE OF HAPTEN CONJUGATION AND THE IMMUNOGENICITY OF DINITROPHENYLATED POLYMERIZED FLAGELLIN
title_short INDUCTION OF IMMUNITY AND TOLERANCE IN VITRO BY HAPTEN PROTEIN CONJUGATES : I. THE RELATIONSHIP BETWEEN THE DEGREE OF HAPTEN CONJUGATION AND THE IMMUNOGENICITY OF DINITROPHENYLATED POLYMERIZED FLAGELLIN
title_sort induction of immunity and tolerance in vitro by hapten protein conjugates : i. the relationship between the degree of hapten conjugation and the immunogenicity of dinitrophenylated polymerized flagellin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2139147/
https://www.ncbi.nlm.nih.gov/pubmed/5062922
work_keys_str_mv AT feldmannmarc inductionofimmunityandtoleranceinvitrobyhaptenproteinconjugatesitherelationshipbetweenthedegreeofhaptenconjugationandtheimmunogenicityofdinitrophenylatedpolymerizedflagellin