Screening strategy for the selection of Leishmania spp. epitopes in humans through molecular interactions analysis: A bioinformatics approach

Introduction: The Leishmania parasite is phagocytized by macrophages and stored in the parasitophorous vacuole; therefore, the activation of Th1-CD4+ lymphocytes is essential to control the infection. Consequently, antigen presentation is critical for such activation, occurring through the binding of short parasite sequences to the MHC class II pocket. Objective: To identify linear sequences from immunogenic proteins of Leishmania (Viannia) spp. through bioinformatic analysis of human MHC class II molecules. Materials and methods: Linear sequences of GP63, HSP70, and PEPCK were obtained from Leishmania panamensis, and the binding of 15-mer peptides to various HLA-DRβ*04 alleles was predicted. Highly conserved sequences among parasite species with null or low analogy to human proteins were selected. Finally, molecular docking was performed against the HLA-DRβ*04:01 pocket. Results: Six sequences were initially selected as potential natural T-cell epitopes. Among these, GP63267-282, GP63282-297, and PEPCK535-550 demonstrated multiple interactions with the HLA-DR: 04:01 pocket and a consistent N-terminus to C-terminus orientation. Conclusion: Three sequences were identified as potential Leishmania Th1 epitopes; however, in vitro validation is necessary to confirm these findings.