title: Yeast killer toxin-like candidacidal Ab6 antibodies elicited through the manipulation of the idiotypic cascade.
abstract: A mouse anti-anti-anti-idiotypic (Id) IgM monoclonal antibody (mAb K20, Ab4), functionally mimicking a Wyckerhamomyces anomalus (Pichia anomala) killer toxin (KT) characterized by fungicidal activity against yeasts presenting specific cell wall receptors (KTR) mainly constituted by β-1,3-glucan, was produced from animals presenting anti-KT Abs (Ab3) following immunization with a rat IgM anti-Id KT-like mAb (mAb K10, Ab2). MAb K10 was produced by immunization with a KT-neutralizing mAb (mAb KT4, Ab1) bearing the internal image of KTR. MAb K20, likewise mAb K10, proved to be fungicidal in vitro against KT-sensitive Candida albicans cells, an activity neutralized by mAb KT4, and was capable of binding to β-1,3-glucan. MAb K20 and mAb K10 competed with each other and with KT for binding to C. albicans KTR. MAb K20 was used to identify peptide mimics of KTR by the selection of phage clones from random peptide phage display libraries. Using this strategy, four peptides (TK 1-4) were selected and used as immunogen in mice in the form of either keyhole limpet hemocyanin (KLH) conjugates or peptide-encoding minigenes. Peptide and DNA immunization could induce serum Abs characterized by candidacidal activity, which was inhibited by laminarin, a soluble β-1,3-glucan, but not by pustulan, a β-1,6-glucan. These findings show that the idiotypic cascade can not only overcome the barrier of animal species but also the nature of immunogens and the type of technology adopted.
authors.affiliation: Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali, Unità di Microbiologia e Virologia, Università degli Studi di Parma, Parma, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Polonelli
authors.affiliation: Metchnikoff Laboratory, Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, Università degli Studi di Messina, Messina, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Beninati
authors.affiliation: Metchnikoff Laboratory, Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, Università degli Studi di Messina, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Teti
authors.affiliation: Dipartimento di Bioscienze e Territorio (DiBT), Università degli Studi del Molise, Contrada Fonte Lappone, Pesche (IS), Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Felici
authors.affiliation: Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali, Unità di Microbiologia e Virologia, Università degli Studi di Parma, Parma, Italy.
authors.forename: Tecla
authors.initials: T
authors.lastname: Ciociola
authors.affiliation: Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali, Unità di Microbiologia e Virologia, Università degli Studi di Parma, Parma, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Giovati
authors.affiliation: Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali, Unità di Microbiologia e Virologia, Università degli Studi di Parma, Parma, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Sperindè
authors.affiliation: Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi di Messina, Messina, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Lo Passo
authors.affiliation: Dipartimento di Scienze Biologiche ed Ambientali, Università degli Studi di Messina, Messina, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Pernice
authors.affiliation: Metchnikoff Laboratory, Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, Università degli Studi di Messina, Messina, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Domina
authors.affiliation: Metchnikoff Laboratory, Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, Università degli Studi di Messina, Messina, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Arigò
authors.affiliation: Metchnikoff Laboratory, Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, Università degli Studi di Messina, Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Papasergi
authors.affiliation: Metchnikoff Laboratory, Dipartimento di Scienze Pediatriche, Ginecologiche, Microbiologiche e Biomediche, Università degli Studi di Messina, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancuso
authors.affiliation: Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali, Unità di Microbiologia e Virologia, Università degli Studi di Parma, Parma, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Conti
authors.affiliation: Dipartimento di Scienze Biomediche, Biotecnologiche e Traslazionali, Unità di Microbiologia e Virologia, Università degli Studi di Parma, Parma, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Magliani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D002176:Candida albicans / Q000187:drug effects* / Q000276:immunology; D002177:Candidiasis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D005656:Fungal Proteins / Q000737:chemistry / Q000276:immunology; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D006433:Hemocyanins / Q000737:chemistry; D055646:Killer Factors, Yeast / Q000737:chemistry / Q000276:immunology; D051379:Mice; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009183:Mycotoxins / Q000737:chemistry / Q000276:immunology; D019151:Peptide Library; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D010843:Pichia / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D047071:beta-Glucans / Q000737:chemistry / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D005656:Fungal Proteins; D005657:Fungal Vaccines; D055646:Killer Factors, Yeast; D009183:Mycotoxins; D019151:Peptide Library; D010455:Peptides; D011956:Receptors, Cell Surface; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; C044203:anti-IgM; D047071:beta-Glucans; C087906:killer toxin, Pichia; C064197:beta-1,6-glucan; D006433:Hemocyanins; C033363:beta-1,3-glucan; C032808:keyhole-limpet hemocyanin