title: A clonotypic Vγ4Jγ1/Vδ5Dδ2Jδ1 innate γδ T-cell population restricted to the CCR6⁺CD27⁻ subset.
abstract: 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.
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Elham
authors.initials: E
authors.lastname: Kashani
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Föhse
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Solaiman
authors.initials: S
authors.lastname: Raha
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Sandrock
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Oberdörfer
authors.affiliation: 1] Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany [2] Department of Haematology, Haemostasis, Oncology and Stem-Cell Transplantation, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Koenecke
authors.affiliation: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Sebastian
authors.identifier: 0000000195837505
authors.initials: S
authors.lastname: Suerbaum
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Immo
authors.initials: I
authors.lastname: Prinz
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement; D018095:Germ-Line Mutation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D054399:Receptors, CCR6 / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D059010:Single-Cell Analysis; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D013950:Thymus Gland / Q000378:metabolism; D014018:Tissue Distribution; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
chemical_list: C498126:CCR6 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054399:Receptors, CCR6; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D049452:Green Fluorescent Proteins