RA 3077/1-1 Molecular control of gamma delta T cell functions
γδ T cells can be classified through the expression of the given γ- and δ -chains of the γδ T cell receptor (TCR) complex and their localization within the body. As innate lymphocytes they are already at birth highly functional to immediately protect the newborns against pathogenic infections. We assume that extrinsic (self-antigens, microbial exposure) and intrinsic (transcription factors, epigenetic imprinting) factors might fine-tune the development, organ-specificity and functional adaptation of murine and human γδ T cells.
Murine IL-17 producing Vγ6 and Vγ4 T cells develop within an embryonic thymus and are maintained as long-living, tissue-resident cells throughout adulthood. In the first part of this project we aim at understanding how the functional adaptation and maintenance of IL-17 producing γδ T cells within their respective tissue niche is regulated through underlying transcriptional and epigenetic mechanisms.
The second part of this project deals with human γδ T cells. We and other could recently show by next generation sequencing of human γδ TCRs that the adult, but not neonatal, γδ TCR repertoires display a high diversity and consist of individual, expanded γδ T cell clones. Surprisingly we identified shared Vδ2 T cell clones, but no single Vδ1 T cell clone, in neonates and those shared Vδ2 T cell clones are rarely present in adults. We hypothesize that these public Vδ2 T cells are a first set of standard effector cells and are only present in early childhood. Now we aim at characterizing these innate γδ T cell clones via advanced flow cytometric methods, next-generation sequencing technologies and bioinformatics analysis.
This project is part of the research group FOR2799 („Receiving and Translating Signals via the γδ T Cell Receptor“).