Role of PATZ1 for memory CD8+ T cell differentiation

Cytotoxic T cells are an important component of our immune system, and play a central role during anti-viral and anti-tumor immune responses. Upon viral infection or tumor emergence, cytotoxic T cells expand rapidly and eliminate infected cells or tumors. Subsequently, while the majority of activated cytotoxic T cells undergo a contraction phase, a fraction of cells further differentiates into memory T cells, which play an essential role during the secondary immune responses (i.e. the exposure of same/similar viruses or tumors). Therefore, understanding of the molecular and cellular mechanisms underlying the generation of memory T cells is an important topic in immunology and highly relevant for clinical researches, such as designing of vaccines and cancer immunotherapies. In this FWF project, we plan to elucidate the role of the transcription factor AT-hook containing Zinc finger protein 1 (PATZ1) in establishing the subset diversity of memory T cells. By using a mouse model of viral infection, we will comprehensively analyze the impact of PATZ1-deletion on the generation of memory T cells and the secondary immune responses. Moreover, we will utilize state-of-the-art techniques, such as single-cell RNA-sequencing and ATAC-seq assay, and thereby aim to reveal molecular mechanisms by which PATZ1 controls the subset diversity of memory T cells. Finally, by establishing a culturing system to generate memory T cells from human peripheral blood mononuclear cells, we will examine whether PATZ1 exerts similar function in human T cells. We anticipate that our project will provide novel insight into molecular mechanisms governing generation of memory T cells and thereby contribute to the better understanding of our immune system. Moreover, the knowledge obtained from our study could be in the long run translated into new strategies for vaccination and immunotherapies, such as through the intervention of PATZ1 or PATZ1-dependent pathways.