Vaccine potential of HLA‐A2 epitopes from Leishmania Cysteine Protease Type III (CPC)

Abstract

Although the precise host-defence mechanisms are not completely understood, T-cell-mediated immune responses are believed to play a pivotal role in controlling parasite infection. In this study, the potential HLA*A2 restricted peptides were predicted and the ability of peptides to bind HLA-A*02 was confirmed by a MHC stabilization assay. Two of the peptides tested stabilized HLA-A*02: (a) LLATTVSGL (P1) and (b) LMTNGPLEV (P3). The potential of the peptides to generate protective immune response was evaluated in patients with treated visceral leishmaniasis as well as in healthy control subjects. Our data suggest that CD8 T-cell proliferation against the selected peptide was significantly higher compared to unstimulated culture conditions. The stimulation of peripheral blood mononuclear cells with epitopes individually or as a cocktail upregulated IFN-γ production, which indicates its pivotal role in protective immune response. The IFN-γ production was mainly in a CD8 T-cells-dependent manner, which suggested that these epitopes had an immunoprophylactic potential in a MHC class I-dependent manner. Moreover, no role of the CD3 T cell was observed in the IL-10 production against the selected peptides, and no role was found in disease pathogenesis. Further studies on the role of these synthetic peptides may contribute significantly to developing a polytope vaccine idea towards leishmaniasis.

Design of multi-epitope peptides containing HLA class-I and class-II-restricted epitopes derived from immunogenic Leishmania proteins, and evaluation of CD4+ and CD8+ T cell responses induced in cured cutaneous leishmaniasis subjects

“…Most of the studies have focused on the identification of HLA-I epitopes [74][75][76][77][78][79][80] but only a few have been conducted to predict HLA-II [81][82][83] or a combination of both HLA-I and -II epitopes [23,84,85]. In this study, we described peptides containing multiple HLA-I and -II epitopes that would induce both CD8+ and CD4+ T cell responses, crucial for protection.…”

“…Some studies have shown significant levels of IFN-γ and low levels of IL-10 in response to HLA-I or HLA-II restricted epitopes derived from different Leishmania proteins, used alone or as pools, in cured CL or visceral leishmaniasis (VL) individuals [75,77,78,83]. However, only a few studies have focused on the identification of both HLA-I and -II restricted peptides.…”

“…These results suggest that the selected peptides include T cell epitopes that are naturally processed and presented to the immune system during infection. Some studies have shown that HLA-I or HLA-II restricted T cell epitopes derived from L. major or L. donovani proteins, used alone or as pools, were able to activate specific IFN-γ producing CD8+ or CD4+ T cells, in cured VL or CL subjects [75,77,78,80,82]. As far as we know, no study has described the detection of both cell populations in response to stimulation by both HLA-I and -II restricted peptides in humans.…”

Expression of cysteine proteinases and cystatins in parasites and use of cysteine proteinase inhibitors in parasitic diseases. Part III: Protozoa (3): Kinetoplastids

“…Significant potentiality of individual P1 or P3 to generate protective immune response (CD8 + T-cell proliferation) was observed in treated VL patients compared to healthy controls. Development of DNA vaccine against VL employing combined P1 and P3 was recommended [80] .…”

Next Generation Sequence Analysis of Sequences From Sra File of Hiv-1 Envelope Protein.

“…It leads to the creation of a plethora of antigens changing constantly on the surface of viral glycoprotein. Its structural features disguise conserved receptor-binding sites from the immune system, and potential epitopes are shielded from antibodies by the presence of carbohydrate moieties (Stein 1990, Dikhit, Amit et al 2017. The rapid advance of computation work and Bioinformatics approaches has increased our ability to understand HIV-1 structure and antibody approach towards immunogenic design.…”