title: The effect of haptens on protein-carrier immunogenicity.
abstract: The immune response against hapten is T-cell-dependent, and so requires the uptake, processing and presentation of peptides on MHC class II molecules by antigen-presenting cells to the specific T cell. Some haptens, following conjugation to the available free amines on the surface of the carrier protein, can reduce its immunogenicity. The purpose of this study was to explore the mechanism by which this occurs. Four proteins were tested as carriers and six molecules were used as haptens. The immune response to the carrier proteins was reduced > 100-fold by some of the haptens (termed carrier immunogenicity reducing haptens--CIRH), whereas other haptens did not influence the protein immunogenicity (carrier immunogenicity non-reducing haptens--nCIRH). Conjugation of the protein to a CIRH affected protein degradation by lysosomal cathepsins, leading to the generation of peptides that differ in length and sequence from those derived from the same native protein or that protein modified with nCIRH. Injection of CIRH-conjugated protein into mice induced an increase in the population of regulatory T cells. The results of this study provide a putative mechanism of action for the reduction of immune response to haptenated proteins.
authors.affiliation: Department of Animal Sciences, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel; MIGAL - Galilee Technology Centre, Kiryat Shmona, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Gefen
authors.forename: Jacob
authors.initials: J
authors.lastname: Vaya
authors.forename: Soliman
authors.initials: S
authors.lastname: Khatib
authors.forename: Irena
authors.initials: I
authors.lastname: Rapoport
authors.forename: Meital
authors.initials: M
authors.lastname: Lupo
authors.forename: Eilon
authors.initials: E
authors.lastname: Barnea
authors.forename: Arie
authors.initials: A
authors.lastname: Admon
authors.forename: Elimelech Dan
authors.initials: ED
authors.lastname: Heller
authors.forename: Elina
authors.initials: E
authors.lastname: Aizenshtein
authors.forename: Jacob
authors.initials: J
authors.lastname: Pitcovski
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D002403:Cathepsins / Q000276:immunology; D004337:Drug Carriers / Q000494:pharmacology*; D006241:Haptens / Q000276:immunology / Q000494:pharmacology*; D008247:Lysosomes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000276:immunology / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D004337:Drug Carriers; D006241:Haptens; D010455:Peptides; D002403:Cathepsins
keywords: carrier immunogenicity; hapten; peptide repertoire; tolerance