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

Here we investigate the TCR repertoire of mouse Vγ4 + γδ T cells in correlation with their developmental origin and homeostasis. By deep sequencing we identify a high frequency of straight Vδ5Dδ2Jδ1 germline rearrangements without P- and N-nucleotides within the otherwise highly diverse Trd repertoire of Vγ4 + cells. This sequence is infrequent in CCR6 − CD27 + cells, but abundant among CCR6 + CD27 − γδ T cells. Using an inducible Rag1 knock-in mouse model, we show that γδ T cells generated in the adult thymus rarely contain this germline-rearranged Vδ5Dδ2Jδ1 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 Vγ4 + Vδ5 + cells. In conclusion, this study identifies an innate subset of fetal thymus-derived γδ T cells with an invariant Vγ4 + Vδ5 + TCR that is restricted to the CCR6 + CD27 − subset of γδ T cells. Functional diversity of T cells expressing antigen receptors composed of γ and δ chains is just beginning to be appreciated. Here the authors show that within γδ T cells of highly diverse Vγ4+repertoire there is a population with germline rearranged, invariant TCR and a distinct phenotype.