MAPPING OF THE T-CELL EPITOPE IN THE MAJOR 43-KILODALTON GLYCOPROTEINOF PARACOCCIDIOIDES-BRASILIENSIS WHICH INDUCES A TH-1 RESPONSE PROTECTIVE AGAINST FUNGAL INFECTION IN BALB C MICE/

The 43-kDa glycoprotein of Paracoccidioides brasiliensis is the major diagnostic antigen of paracoccidioidomycosis, the prevalent systemic m ycosis of Latin America, Apart from eliciting high antibody titers, gp 13 is also immunodominant in delayed-type hypersensitivity reactions i n infected animals and humans, The cellular immune response in mice to gp43 administered in complete Freund's adjuvant involves CD4(+) Th-l 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-as sisted protein analysis, The structural requirements of the T-cell epi tope were determined by assaying a series of P10 analogous and truncat ed peptides, Only 12-mer or longer sequences were active, confirming p resentation by major histocompatibility complex II, The HTLAIR inner c ore of P10 is the essential domain of the epitope, with various flanki ng regions possible, Immunization of mice with both gp43 and P10 led t o vigorous protection against intratracheal challenge by virulent P. b rasiliensis, with a >200-fold decrease in lung CFU and halting of diss emination to the spleen and liver, The protective effect of P10 is mai nly attributed to an IFN-gamma mediated cellular immune response, Unli ke gp43, which induces an antibody response compatible with both Th-l and Th-2 activation in infected BALB/c mice, P10 does not induce a hum oral response, Protection by gp43 and P10 was characterized by a few w ell-demarcated lung granulomas with numerous nonviable yeast forms or resolved lesions with no detectable fungal cells.