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Parasite Immunol ; 25(4): 199-209, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12940963

ABSTRACT

In vitro peptide binding assays and DCs pulsed with recombinant KMP-11 (rKMP-11) plus six 20-mer overlapping peptides covering the entire protein of Leishmania (Viannia) panamensis (L(V)p) promastigotes were used to identify T-cell epitopes in this protein. Such in vitro binding assays, using HLA DRB1* 0101, -0401, -0701 and -1101 alleles, demonstrated that two peptide sequences (DEEFNKKMQEQNAKFFADKP and FKHKFAELLEQQKAAQYPSK) exhibited high HLA DRB1* 0401 allele binding capacity. rKMP-11 specific T-cell proliferation and cytokine production, derived from 13 volunteers exposed to the parasite, suggested that using autologous DCs as APCs becomes advantageous in uncovering T-cell epitopes promoting proliferation and differences in IFN-gamma and IL-4 production in T-cells from volunteers with ACTIVE and CURED undetectable disease when other APCs were used. The two peptides which bound in vitro to the HLA DRB1* 0401 allele were immunogenic in HLA DRB1* 04 volunteers, thus validating the use of in vitro binding assays for predicting epitopes in this protein. The experimental approach used here may prove useful for characterizing T-cell epitopes in a protein useful in designing peptide-based vaccine candidates for Leishmania and other intracellular pathogens.


Subject(s)
Immunity, Cellular , Leishmania guyanensis/immunology , Leishmaniasis, Mucocutaneous/immunology , Membrane Proteins/immunology , Protozoan Proteins/immunology , Amino Acid Sequence , Animals , Antigen Presentation , Antigens, Protozoan/genetics , Binding, Competitive , Case-Control Studies , Cell Line , Cytokines/biosynthesis , Dendritic Cells/immunology , Epitope Mapping , Epitopes/genetics , Female , HLA-DR Antigens/metabolism , HLA-DRB1 Chains , Humans , In Vitro Techniques , Leishmania guyanensis/genetics , Lymphocyte Activation , Male , Membrane Proteins/genetics , Molecular Sequence Data , Protozoan Proteins/genetics , T-Lymphocytes/immunology
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