Yeast killer toxin-like candidacidal Ab6 antibodies elicited through the manipulation of the idiotypic cascade.

Luciano Polonelli,Ida Pernice,Milena Arigò,Franco Felici,Walter Magliani,Martina Sperindè,Laura Giovati,Carla Lo Passo,Maria Domina,Stefania Conti,Concetta Beninati,Salvatore Papasergi,Tecla Ciociola,Giuseppe Teti,Giuseppe Mancuso,Eric A Johnson

doi:10.1371/journal.pone.0105727

Luciano Polonelli, Ida Pernice + Show 14 more

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https://doi.org/10.1371/journal.pone.0105727

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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.

Highlights

The concept of idiotypy could be dated back to the beginning of the XX century when Paul Ehrlich and others predicted that antibodies (Abs) may be directed against the combining regions of other Abs
In a previous work we described a rat anti-Id mAb representing the internal image of a killer toxin (KT, Ag), produced by the yeast Wyckerhamomyces anomalus (Pichia anomala) ATCC 96603, characterized by fungicidal activity against Candida albicans cells bearing specific KT cell wall receptors (KTR) [14]
MAb K20 proved to bind to C. albicans cell wall, to germ tubes and budding cells (Figure 1)

Summary

Introduction

The concept of idiotypy could be dated back to the beginning of the XX century when Paul Ehrlich and others predicted that antibodies (Abs) may be directed against the combining regions of other Abs. At that time, nothing was known about the molecular properties of Abs and the vague term ‘‘side chain’’ was used to define particular chemical structures of the combining site (afterwards referred to as idiotype, Id) which could account for differences in its specificity [1]. There have been numerous reports on the interaction of anti-Ids with cellular receptors for a variety of external Ags [13]. The interaction with cellular receptors, especially if the appropriate biological effects are mediated, is perhaps more convincing than the induction of Abs as evidence for the structural relatedness of Ag and anti-Id

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