INHIBITORY EFFECT OF HUMAN NATURAL YEAST KILLER TOXIN-LIKE CANDIDACIDAL ANTIBODIES ON PNEUMOCYSTIS-CARINII

Background: Human natural antibodies have been found that owe their ca ndidacidal action to the mimicry of a yeast killer toxin produced by t he yeast Pichia anomala (PaKT). Candidacidal human natural antibodies (KTAb) are elicited by and bind to a KT receptor (PaKTR) present on th e cell surface of infectious PaKT-sensitive microorganisms. Because of the recognized susceptibility of Pneumocystis carinii organisms to Pa KT upon the occurrence of specific PaKTR, we examined whether human na tural KTAb could also bind to and inhibit P. carinii. Materials and Me thods: Immunoaffinity-purified KTAb from the vaginal fluid of patients affected by candidiasis were tested and compared with PdKT for their ability to inhibit rat-derived P. carinii attachment to epithelial lun g cells as well as infectivity to nude rats. Immunofluorescence studie s were also performed by biotinylated PaKT in competition with human K TAb to establish their specific binding to PaKTR on the surface of rat -derived and human P. carinii organisms. Results: Human natural candid acidal KTAb exerted a strong, specific inhibitory activity against rat -derived P. carinii organisms that are susceptible to PaKT itself. The antimicrobial activity of human KTAb was abolished by adsorption with a specific PaKT-neutralizing mAb KT4. Immunofluorescence studies of c ompetition with PaKT showed that human KTAb efficiently bind to the sp ecific PaKTR on the surface of rat-derived and human P. carinii organi sms. Conclusions: The results strongly suggest that human KTAb, elicit ed by a common transphyletic receptor of different pathogenic microorg anisms during infection, may play a role in antibody-mediated cross-im munity and, if properly engineered, as functionally equivalent recombi nant antibodies they could exert a therapeutic activity against pneumo cystosis in vivo.