Carrier-induced, hapten-specific suppression: a problem of antigen presentation?
Prior immunity against a carrier protein has been shown to modulate the serologic response to injected haptens attached to the same carrier. In particular, a carrier/hapten-carrier immunization protocol induces marked suppression for IgG2a anti-hapten Ab production but does not interfere with anti-carrier Ab responses. Although the phenomenon of epitopic suppression has been amply demonstrated, the mechanism underlying the suppression remains unknown. The selective deficiency in IgG2a secretion suggests that IFN-gamma-producing Th1 cells are not properly activated. We and others have shown that the nature of the APCs present during the first encounter with the Ag influences the development of selected Th populations in vivo; dendritic cells (DCs) seem to be required for the induction of primary, Th1-type responses. Since carrier priming induces the clonal expansion of specific B cells that appear to efficiently capture the Ag, we hypothesized that the hapten-carrier conjugate may be presented by B cells in preimmunized animals. Therefore, we immunized mice to the conjugate by injecting syngeneic DCs pulsed in vitro with the Ag. Our data show that an injection of DCs and IL-12 prevents epitopic suppression, suggesting that it may result from defective Ag presentation.
Département de Biologie Moléculaire, Université Libre de Bruxelles, Rhode-Saint-Genèse, Belgium.
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Renjifo
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Wolf
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Pastoret
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Bazin
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Urbain
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Leo
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Moser
D000818:Animals; D017951:Antigen Presentation; D000955:Antigens, T-Independent / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000008:administration & dosage / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D007165:Immunosuppression Therapy; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D010851:Picrates / Q000008:administration & dosage / Q000276:immunology
D000955:Antigens, T-Independent; D002352:Carrier Proteins; D000939:Epitopes; D006241:Haptens; D007074:Immunoglobulin G; D010851:Picrates; C054401:trinitrophenyl keyhole limpet hemocyanin; D018664:Interleukin-12; D006433:Hemocyanins