Identification of immunogenic T-cell peptides of Mycobacterium tuberculosis PE_PGRS33 protein

Abstract

The development of a more efficient vaccine is needed to improve tuberculosis control. One of the current approaches is to identify immunogenic T-cell peptides that can elicit a protective and specific immune response. These peptides come from immunogenic proteins of the pathogen. The PE_PGRS33 protein of Mycobacterium tuberculosis has been proved immunogenic. However, little is known about immunogenic T-cell peptides of PE_PGRS33 and their interactions with MHC-II molecules. Therefore, we used the SYFPHEITHI database to determine the immunogenic PE_PGRS33 T-cell peptides. Next, we built homology models by using MOE v2018.1 software in order to obtain information about the specific interactions between the peptides and I-A^k. The AlgPred server was employed to look for allergenic sites in PE_PGRS33. We developed a sequence alignment between PE_PGRS33 and all the human proteins by using BLAST. Three peptides were commercially synthesized, and their activity was evaluated in vitro by the stimulation of PBMC from household contacts of TB patients. Our in silico results showed five immunogenic T-cell peptides. BLAST analysis showed low homology of PE_PGRS33 with human proteins and AlgPred did not reveal allergenic sites in PE_PGRS33. The three peptides triggered the activation of CD4⁺ T cells from the households contacts, showed by the production of IFN-γ. We identified three immunogenic peptides of PE_PGRS33 that demonstrated activity in vitro which allows to deepen into the immune response towards mycobacterial antigens, moving forward to the identification of new vaccine candidates.

Keywords: Bioinformatics; Immunogenic peptide; Mycobacterium tuberculosis; PE_PGRS33; Tuberculosis.