Immunodominant epitopes from Paracoccidioides brasiliensis identified.

2004 SEP 1 - (NewsRx.com & NewsRx.net) -- In silico prediction of peptides binding to multiple HLA-DR molecules accurately identifies immunodominant epitopes from gp43 of Paracoccidioides brasiliensis frequently recognized in primary peripheral blood mononuclear cell responses from sensitized individuals.

"One of the major drawbacks limiting the use of synthetic peptide vaccines in genetically distinct populations is the fact that different epitopes are recognized by T cells from individuals displaying distinct major histocompatibility complex molecules. Immunization of mice with peptide (181-195) from the immunodominant 43-kDa glycoprotein of Paracoccidioides brasiliensis (gp43), the causative agent of paracoccidioidomycosis (PCM), conferred protection against infectious challenge by the fungus," scientists in Brazil and the United States report.

"To identify immunodominant and potentially protective human T-cell epitopes in gp43, we used the TEPITOPE algorithm to select peptide sequences that would most likely bind multiple HLA-DR molecules and tested their recognition by T cells from sensitized individuals," said Leo Kei Iwai at the Federal University of Sao Paulo and collaborators in Brazil and the U.S. "The five most promiscuous peptides were selected from the gp43 sequence and the actual promiscuity of HLA binding was assessed by direct binding assays to nine prevalent HLA-DR molecules. Synthetic peptides were tested in proliferation assays with peripheral blood mononuclear cells (PBMC) from PCM patients after chemotherapy and healthy controls."

"PBMC from 14 of 19 patients recognized at least one of the promiscuous peptides, whereas none of the healthy controls recognized the gp43 promiscuous peptides," reported the researchers. "Peptide gp43[subscript]180-194 was recognized by 53% of patients, whereas the other ...