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Uncovering the epitopes underlying the induction of varying adaptive immune responses by different Mycobacterium tuberculosis lineages

AuthorsMagalhães, Carlos; Comas, Iñaki ; Saraiva, Margarida; Osório, Nuno S.
Issue Date19-Sep-2019
CitationScientific Meeting on Mycobacteria. MycoPORTO 2019 Porto (Portugal)
AbstractPág. 22 del libro de abstracts. Tuberculosis (TB) is the deadliest infectious disease in the history of humankind and remains vastly uncontrolled. Active TB results from infection with distinct genetic lineages of the Mycobacterium tuberculosis complex. Interestingly, a strong geographic association between TB cases and specific lineages exists, which is disrupted in the context of HIV-1 co-infection. This fact highlights the relevance of CD4+ T cell-driven immune responses in the interaction between different human/pathogen populations and TB outcome. We have developed a genome-wide immunoinformatics approach to identify CD4+ T cell epitopes that are influenced by the presence of M. tuberculosis lineage-specific polymorphisms. Results showed several amino acid substitutions with distinct and significant impacts in the interaction with globally abundant human leukocyte antigen (HLA) alleles. Ongoing in vitro validation enabled the identification of a Lineage 1-restricted mutant peptide that binds HLA-DRB1*01:01 with high affinity and stability, comparatively similar to an immunodominant epitope from ESAT-6 antigen. Overall, this study suggests that specific M. tuberculosis lineage-restricted polymorphisms have been selected during evolution with the host due to CD4+ T cell pressure. The identification and extensive characterization of varying M. tuberculosis epitopes might be of great relevance for the development of more effective TB vaccination and diagnostics strategies.
DescriptionAbstract de la comunicación oral presentada al Scientific Meeting on Mycobacteria. MycoPORTO 2019 Porto (Portugal), 19-20 de septiembre de 2019
Appears in Collections:(IBV) Comunicaciones congresos
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