Investigating in the implications of the ?d T cell receptor in the acquisition of IL-17 producing effector functions

One common way to classify functional ?d T cell subsets is based on the expressed variable gene region of the T-cell-receptor (TCR) ?-chain. It is established that the TCRs of murine IL-17 producing ?d T cells are either V?6+ or V?4+. The majority of IL-17 producers get functionally pre-programmed in the prenatal thymus, and persist thereafter as tissue-resident cells into adulthood. Little is known about the role of the expressed TCR on IL-17 effector fate acquisition, and if also other subsets can produce IL-17 under certain circumstances. To address this question, we took advantage of a mouse model that lack the V?4 and V?6 ?-chain (V?4-/- / V?6-/- double knock-out). Initial results indicate that V?1+ T cells show increased IL-17 production capability in the absence of V?4+ and V?6+ ?d T cells, suggesting that the ?dTCR does not always instruct the phenotype. This raises the question about the ontogenetic origin, which might be a TCR-independent default mechanism to instruct IL-17 production by ?d T cells, of IL-17+ V?1+ T cells. Moreover, it remains elusive if these V?1+ T cells (i) adopt highly similar tissue-specific gene expression programs and (ii) functionality in health and disease, than the V?4+ and V?6+ T cells. Overall design: To elucidate whether IL-17pos and IL-17neg V?1+ T cells show a similar or a different TCR repertoire diversity, an mRNA-based next-generation sequencing analysis of d-chain sequences (TCR-seq) was performed on FACS-sorted IL-17pos and IL-17neg ?d T cells from pLNs of V?4-/- / V?6-/- mice.