Characterizing cellular immune response to kinetoplastid membrane protein‐11 (KMP‐11) during Leishmania (Viannia) panamensis infection using dendritic cells (DCs) as antigen presenting cells (APCs)

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.

HLA Class I–Restricted T Cell Epitopes of the Kinetoplastid Membrane Protein–11 Presented byLeishmania donovani–Infected Human Macrophages

“…The epitope map for L. donovani kmp-11 established with the work presented here should significantly facilitate the study of the role of CD8 + T cells in human leishmaniasis and could serve for monitoring function-related phenotypes and functional capacities of the T cells in patients with various clinical conditions. A corresponding mapping of kmp-11 epitopes for CD4 + T cells has been reported by Delgano et al [26]. These authors used T cells from 13 individuals cured of L. panamensis infection, and they found 2 active peptides presented by a single HLA class II allomorph.…”

Experimental Validation of Multi-Epitope Peptides Including Promising MHC Class I- and II-Restricted Epitopes of Four Known Leishmania infantum Proteins

“…Previous studies concerning the identification of T cell epitopes using infected macrophages or DCs as APCs, revealed the existence of potential HLA class I- and II-restricted T cell epitopes in the amino-terminal region, characterizing a dominant cluster between position 1 and 33 of KMP-11 sequence that could trigger specific cellular immune responses in L. donovani - or L. panamensis -infected volunteers (80, 81). Furthermore, hybrid-cell, DNA-based or heterologous KMP-11-DNA/rVV based vaccination exhibited immunoprotective capacity in susceptible VL murine models.…”

Immunopathogenic competences ofLeishmania(V.)braziliensisandL.(L.)amazonensisin American cutaneous leishmaniasis

“…it was strongly demonstrated the ability of L. ( V. ) braziliensis or L. ( L. ) amazonensis in directing the immune response dichotomy of human infection by these Leishmania parasites. Clearly, these considerations can also be applied to other neotropical Leishmania species closely related to the mentioned species; L. ( V. ) panamensis and L. ( L. ) mexicana , principally, in view of their immunopathogenic competences to be similar to those of L. ( V. ) braziliensis and L. ( L. ) amazonensis , respectively (58–61).…”