A clonotypic Vγ4Jγ1/Vδ5Dδ2Jδ1 innate γδ T-cell population restricted to the CCR6+CD27− subset

Abstract

Here we investigate the TCR repertoire of mouse Vg4 þ gd T cells in correlation with their developmental origin and homeostasis. By deep sequencing we identify a high frequency of straight Vd5Dd2Jd1 germline rearrangements without P-and N-nucleotides within the otherwise highly diverse Trd repertoire of Vg4 þ cells. This sequence is infrequent in CCR6 À CD27 þ cells, but abundant among CCR6 þ CD27 À gd T cells. Using an inducible Rag1 knock-in mouse model, we show that gd T cells generated in the adult thymus rarely contain this germline-rearranged Vd5Dd2Jd1 sequence, confirming its fetal origin. Single-cell analysis and deep sequencing of the Trg locus reveal a dominant CDR3 junctional motif that completes the TCR repertoire of invariant Vg4 þ Vd5 þ cells. In conclusion, this study identifies an innate subset of fetal thymus-derived gd T cells with an invariant Vg4 þ Vd5 þ TCR that is restricted to the CCR6 þ CD27 À subset of gd T cells.

IL ‐7‐dependent compositional changes within the γδ T cell pool in lymph nodes during ageing lead to an unbalanced anti‐tumour response

“…1 0 Next, we assessed the recombination of TCRd chains and observed distinct preferences in the choice of Vd segments amongst the different subsets ( Fig 4B). In young mice, TCRd chains utilised by Vc1 + cd1 T cells contained mainly rearrangements with Vd6 (~40%) and Vd2 (~30%) segments, followed by Vd7 (~10%), Vd5 (~10%), Vd4 (~7%) and Vd3 (~3%), consistent with a previous study [48]. In old mice, the use of Vd6 increased slightly to~50% and the use of Vd2 decreased marginally to~25% compared with young mice (Fig 4B, upper-left panel).…”

“…In old mice, the use of Vd6 increased slightly to~50% and the use of Vd2 decreased marginally to~25% compared with young mice (Fig 4B, upper-left panel). In young mice, the majority of TCRd chains from the Vc4 + cd1 T-cell samples contained a Vd7 segment (~75%), followed by Vd5 (~10%), Vd6 (~8%) and Vd4 (~7%) again similar to observations in a previous study [48] ( Fig 4B, upper-right panel). In old mice, the preferential use of Vd7 by Vc4 + cd1 T cells was slightly reduced to~70% ( Fig 4B, upperright panel).…”

“…Furthermore, we identified two CDR3 clones from separate mice with different nucleotide sequences both giving rise to an emerging Vd4 + clone with CALMERDIGGIRATDKLVF amino acid sequence ( Fig 4C). Most interestingly, we detected the canonical ASGYIGGIRATDKLV (Vc4Jc1/Vd5Dd2Jd1) clone [48] in all individuals and found that this dominant clone in young mice decreases over 50% in 3 out of 4 old mice.…”

Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance

“…Although γδ T cells recognize target cells in an MHC-independent fashion, consistent with a lack of surface CD4/CD8αβ co-receptor expression, the key paradigms underpinning their distinct immunobiology are unclear. Mouse studies have highlighted γδ T cell subsets bearing semi-invariant TCRs1345, suggestive of an innate-like biology and a limited range of self-ligands. In humans the Vδ2 + repertoire predominant in peripheral blood arguably conforms to this paradigm.…”

Bohemian T cell receptors: sketching the repertoires of unconventional lymphocytes

“…Their name comes from their ability to rapidly produce IL-17A in response to a broad array of infectious and non-infectious agents. By sequencing the TCRδ genes paired to Vγ4+ cells, Kashani and colleagues found a high proportion of clones used a germline Vδ5-Dδ2-Jδ1 rearrangement, and this clone acquires an innate-like (IL-17A+ CCR6+ CD27−) phenotype with widespread tissue distribution, categorically placing them into the natural Tγδ17 cells (31). Consistent with this finding, single-cell TCR sequencing of the IL-23R+ natural Tγδ17 cells from multiple tissues identified the same Vγ4Vδ5+ clonotypes (32).…”