INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
IDENTIFICATION OF POTENTIAL SHARED EPITOPES BETWEEN T. cruzi AND THE B16-F10 TUMOR CELL LINE
CARRI, IBEL; KAUFMAN, CINTIA DANIELA; NIELSEN, MORTEN; BRACCO, LEONEL
Mar del Plata
Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022
Spontaneous regression of cancer is often associated with infections. Pre- existing memory T lymphocytes generated in response to microorganisms could recognize tumor antigens that share sequences with microbial epitopes. We have observed that both the infection with Trypanosoma cruzi the etiological agent of Chagas Disease and the immunological memory generated in response to the infection, inhibit tumor growth in C57BL/6 mice challenged with B16-F10 cells (murine metastatic melanoma). To predict and identify potential MHC class I epitopes shared between the parasite and the tumor, we downloaded sequences of the whole exome of B16-F10 cells and C57BL/6 mice from the European Nucleotide Archive. After initial quality control, data were processed to obtain BAM files for variant analysis with Mutect2. Peptides of 8 to 11 residues that are potential ligands of H2-Db and H2-Kb alleles were found employing Mupexi, a tool that uses NetMHCpan 4.0 for the prediction. Neoepitopes were confirmed with the last available version of NetMHCpan (4.1). Additionally, mimotopes were generated by changing the aminoacidic residues of the anchor positions that do not interact with the TCR but determine binding to the MHC, for only those that can be in those positions (L, I, V & M and L, I, V, M & F in position 8 of the ligands of H2-Db and H2-Kb, respectively). BLASTP was used to search at the 100% similarity level the tumor epitopes and mimotopes in the proteome of different strains of T. cruzi. We have observed that proteins which are key for tumoral progression, such as SOX-21, CENPF, CLIP, SPON1 and DIP2A, could be immunogenic and shared peptides with T. cruzi. Interestingly, among parasite antigens that shared peptides with tumor antigens we found trans-sialidase family members, an important virulence factor and promising target for vaccines.