IAI FigSearch
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Taborda, C. P.
Right arrow Articles by Travassos, L. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Taborda, C. P.
Right arrow Articles by Travassos, L. R.

 Previous Article  |  Next Article 

Infect Immun, February 1998, p. 786-793, Vol. 66, No. 2
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Mapping of the T-Cell Epitope in the Major 43-Kilodalton Glycoprotein of Paracoccidioides brasiliensis Which Induces a Th-1 Response Protective against Fungal Infection in BALB/c Mice

Carlos P. Taborda,1 Maria A. Juliano,2 Rosana Puccia,1 Marcello Franco,3 and Luiz R. Travassos1,*

Discipline of Cell Biology, Department of Microbiology, Immunology, and Parasitology,1 and Departments of Biophysics2 and Pathology,3 Federal University of São Paulo, São Paulo, Brazil

Received 6 August 1997/Returned for modification 30 September 1997/Accepted 7 November 1997

The 43-kDa glycoprotein of Paracoccidioides brasiliensis is the major diagnostic antigen of paracoccidioidomycosis, the prevalent systemic mycosis of Latin America. Apart from eliciting high antibody titers, gp43 is also immunodominant in delayed-type hypersensitivity reactions in infected animals and humans. The cellular immune response in mice to gp43 administered in complete Freund's adjuvant involves CD4+ Th-1 lymphocytes, secreting gamma interferon (IFN-gamma ) and interleukin 2 (IL-2) but not IL-4 and IL-10. The T-cell epitope of this antigen was mapped to a 15-amino-acid peptide (P10) based on lymphoproliferations with primed cells from three different haplotypes and on a computer-assisted protein analysis. The structural requirements of the T-cell epitope were determined by assaying a series of P10 analogous and truncated peptides. Only 12-mer or longer sequences were active, confirming presentation by major histocompatibility complex II. The HTLAIR inner core of P10 is the essential domain of the epitope, with various flanking regions possible. Immunization of mice with both gp43 and P10 led to vigorous protection against intratracheal challenge by virulent P. brasiliensis, with a >200-fold decrease in lung CFU and halting of dissemination to the spleen and liver. The protective effect of P10 is mainly attributed to an IFN-gamma -mediated cellular immune response. Unlike gp43, which induces an antibody response compatible with both Th-1 and Th-2 activation in infected BALB/c mice, P10 does not induce a humoral response. Protection by gp43 and P10 was characterized by a few well-demarcated lung granulomas with numerous nonviable yeast forms or resolved lesions with no detectable fungal cells.


* Corresponding author. Mailing address: Disciplina de Biologia Celular, Universidade Federal de São Paulo, Rua Botucatu 862/8 andar, São Paulo, SP 04023-062, Brazil. Phone: 55-11-5084-2991. Fax: 55-11-5715877. E-mail: travassos.dmip{at}epm.br.




This article has been cited by other articles:




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 1998 by the American Society for Microbiology. All rights reserved.