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Functional Diversity of T cells

Periodic Reporting for period 2 - FunDiT (Functional Diversity of T cells)

Reporting period: 2020-07-01 to 2021-12-31

T-cell is a type of white blood cells, playing a key role in adaptive immunity. The project FunDiT addresses the diversity of T cells. It is known that T cells represent a heterogeneous compartment with individual populations with unique functions. However, the functional diversity of T cells is poorly understood. Defining individual T-cell subsets and their unique functions will improve our understanding of the immune responses to infection, cancer as well as pathological autoimmune responses.
We established the analysis of gene expression profiling on a single cell level in our laboratory. The results revealed novel T-cell subsets that were not previously described. Using our own data and publicly available data, we generated an atlas of steady-state CD8+ T cells and an atlas of CD8+ T cells during anti-viral responses. We further explored the diversity of CD8+ T cells by characterizing antigen-inexperienced memory-like T cells from different mouse strains, different conditions and even in feral mice. We also characterized the role of coreceptor-LCK interaction in setting up the level of self-reactivity of CD4+ and CD8+ T cells.

We developed a unique mouse model that enables switching the T-cell specificities towards our model antigen. This mouse model will enable us to overcome technical difficulties in studying functional differences between T-cell subsets.

We identified a novel protein species as a negative regulator of signaling via costimulatory T cell receptors and we are studying the physiological relevance of this regulation. We described the mechanism how cells response to IL-17, which can protect the body from fungal infections, but can also induce immune pathology like psoriasis. Moreover, we discovered a novel subunit of IL-17 receptor.
We developed novel bioinformatic tools to study functional differences between T-cell subtypes. We developed and optimized novel techniques for the analysis of immune signaling pathways. We developed a unique mouse model for studying steady-state T-cell functional diversity. We expect to identify novel cellular and molecular mechanisms contributing to the effective protective immune responses and/or to immune self-tolerance.
T cell diversity revealed by single cell transcriptomics