The gp43 from Paracoccidioides brasiliensis: A Major Diagnostic Antigen and Vaccine Candidate
The gp43, a 43,000 dalton glycoprotein from Paracoccidioides brasiliensis, is one of those rare examples of a major diagnostic antigen in serological assays (e.g., Mendes-Giannini et al. 1990) that also contains epitopes eliciting an immunoprotective cell
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CONTENTS I. 11.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . Discovery, Purification and Properties of gp43 .............................. A. Discovery of gp43 . . . . . . . . . . . . . . . . . . . . . . B. Purification of gp43 .................... C. Adhesion Properties of the gp43 .......... 111. Serological Assays Using the gp43 . . . . . . . . . A. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . B. Epitopes in the gp43 Reacting with Antibodies ....................... C. Anti-idiotypic Antibodies . . . . . . . . . . . . . . . . IV. Structure of the N-Linked Glycan of the gp43 ........................... V. Cloning of the gp43 Gene and Pro tein Sequencing . . . . . . . . . . . . . . . . . A. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . B. Polymorphism of the gp43 Gene ..... . . . . . VI. Mapping of the T-CeU Epitope in the gp43 ........................... A. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . B. Immunoprotection Elicited by gp43 and PlO ....................... C. Human T-Cell Epitopes in the gp43 . . . . . . . . VII. Immunoprotection by DNA Vaccine Carrying the gp43 Gene . . . . . . . . . . . . . . . . . VIII. Perspectives .......................... References . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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I. Introduction The gp43, a 43,000 dalton glycoprotein from Paracoccidioides brasiliensis, is one of those rare exampIes of a major diagnostie antigen in serologieal assays (e.g., Mendes-Giannini et al. 1990) that also contains epitopes eliciting an immunoprotective cellular immune response. Its role in fungal virulence is not dearly defined which raises the questi on as to the selective pressure that keeps its 1 Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Säo Paulo (UNIFESP), SP 04023-062, Brazil 2 Departamento de Microbiologia, Universidade de Säo Paulo (USP), SP 05508-900, Brazil 3 Laborat6rio de Imunologia, INCOR, USP, Säo Paulo, SP, Brazil
expression constant in both yeast and mycelium phase of this dimorphie pathogenie species. This glycoprotein is also an unusual example of a molecule from a fungal pathogen that had its structure, induding both peptide and carbohydrate constituents, completely defined with respect to linear nonconformational sequences. Whereas the conformational epitopes that bind to antibodies have not been identified, those eliciting an MHC dass II-restricted T-helper lymphocyte proliferation have been mapped in both murine and human systems. Other properties of the gp43, such as laminin bin ding, stabilization of proteolytic enzymes and effects on macrophages, have been suggested, but their relevance to the progression of fungal growth is uncertain. Gp43-deficient mutants have not been produced thus far, therefore a direct appraisal of the overall importance of this molecule for the in vivo growth, survival and dissemination of P. brasiliensis is not possible at present.
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