Immuno-informatics based approaches to identify CD8+ T cell epitopes within the Leishmania donovani 3-ectonucleotidase in cured visceral leishmaniasis subjects |
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| Affiliation: | 1. Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna, 800007, India;2. Department of Biotechnology, National Institutes of Pharmaceutical Education and Research, Hajipur, 844102, India;3. Dept. of Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Patna, 800007, India;4. Dept. of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Patna, 800007, India;5. Department of Bioinformatics, Rajendra Memorial Research Institute of Medical Sciences, Patna, 800007, India;6. Department of Pharmacoinformatics, National Institutes of Pharmaceutical Education and Research, Hajipur, 844102, India;1. Center of Technological Development in Health (CDTS)/National Institute of Science and Technology for Innovation on Neglected Diseases (INCT-IDN), FIOCRUZ, Rio de Janeiro, RJ, Brazil;2. Laboratory of Experimental and Computational Biochemistry of Pharmaceuticals, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil;3. Hantavirus and Rickettsia Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil;4. Department of Cellular and Molecular Biology, Biology Institute, Federal University Fluminense, Niterói, RJ, Brazil;1. Infectious Diseases Division, CSIR- Indian Institute of Integrative Medicine, Jammu 180001, India;2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India;1. Laboratory of Molecular Biochemistry and Cell Biology, Department of Biochemistry, Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), Agamkuan, Patna 800007, India;2. Biomedical Informatic Centre, Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), Agamkuan, Patna, India;3. Department of Immunology, Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), Agamkuan, Patna, India;4. Department of Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), Agamkuan, Patna, India;5. Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences (RMRIMS), Agamkuan, Patna, India;1. Laboratory of Molecular Biochemistry and Cell Biology, Department of Biochemistry, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna 800007, India;2. Department of Molecular Biology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna 800007, India;3. Department of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna 800007, India;4. Department of Clinical Medicine, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna 800007, India;5. Department of Biotechnology, National Institute of Pharmaceutical Education and Research, EPIP Complex, Hajipur 844102, India |
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| Abstract: | Leishmaniases are vector-borne diseases for which no vaccine exists. These diseases are caused by the Leishmania species complex. Activation of the CD8+ T cell is crucial for protection against intracellular pathogens, and peptide antigens are attractive strategies for the precise activation of CD8+ T in vaccine development against intracellular infections. The traditional approach to mine the epitopes is an arduous task. However, with the advent of immunoinformatics, in silico epitope prediction tools are available to expedite epitope identification. In this study, we employ different immunoinformatics tools to predict CD8+ T cell specific 9 mer epitopes presented by HLA-A*02 and HLA-B40 within the highly conserved 3′-ectonucleotidase of Leishmania donovani. We identify five promiscuous epitopes, which have no homologs in humans, theoretically cover 85% of the world's population and are highly conserved (100%) among Leishmania species. Presentation of selected peptides was confirmed by T2 cell line based HLA-stabilization assay, and three of them were found to be strong binders. The in vitro peptide stimulation of peripheral blood mononuclear cells (PBMC) from cured HLA-A02+ visceral leishmaniasis (VL) subjects produced significantly higher IFN-γ, IL-2 and IL-12 compared to no peptide control healthy subjects. Further, CD8+ cells from treated VL subjects produced significantly higher intracellular IFN-γ, lymphocyte proliferation and cytotoxic activity against selected peptides from the PBMCs of treated HLA-A02+ VL subjects. Thus, the CD8+ T cell specific epitopes shown in this study will speed up the development of polytope vaccines for leishmaniasis. |
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| Keywords: | Vaccine Epitope Immunoinformatics 3′-ectonucleotidase |
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