Mycobacterium tuberculosis, the cause of tuberculosis, has been a pathogen in humans since ancient times and continues to be one of the deadliest and most widespread diseases. M. tuberculosis, and mycobacteria in general, have immense biochemical resilience due to their peculiar outer waxy layer comprised of mycolic acid (MA) and its derivatives. Humans possess T cells that target these lipids, highlighting their potential as a promising vaccine modality. However, as these T cells are absent in mice, a comprehensive understanding of their contribution during infection has not yet been achieved. To date, due to a limited number of MA-reactive TCR clonotypes having been identified, the precise characteristics of MA-reactive T cells remain poorly understood. In this study, using an integrated, multilayered clonotypic approach, including tetramer sorting, single-cell TCR/RNA sequencing, bioinformatic prediction, and TCR reconstitution, the researchers identified four previously unreported MA-reactive TCRs from healthy donors. These findings indicate that science has only just begun to characterize these mycolic acid-reactive T cells, and there may still be many left to be identified. Analyzing additional donors can expand the understanding of the characterization of these lipid-reactive T cells and how the human immune system responds to M. tuberculosis infection.
The level of autonomy I experienced as an undergraduate researcher was unprecedented. I was able to develop new methods and become a true member of the university’s research community, while being abroad allowed me to focus solely on my work. An unexpected highlight was the community I found along the way. From fellow undergraduates to outstanding postdocs at the university and conferences, I formed lifelong friendships and international connections that mean no matter where I go in the world, I will always have someone to call.
Victor De Oliveira