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

Elham Kashani, Lisa Föhse, Solaiman Raha, Inga Sandrock, Linda Oberdörfer, Christian Koenecke, Sebastian Suerbaum, Siegfried Weiss and Immo Prinz ()
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Elham Kashani: Institute of Immunology, Hannover Medical School
Lisa Föhse: Institute of Immunology, Hannover Medical School
Solaiman Raha: Institute of Immunology, Hannover Medical School
Inga Sandrock: Institute of Immunology, Hannover Medical School
Linda Oberdörfer: Institute of Immunology, Hannover Medical School
Christian Koenecke: Institute of Immunology, Hannover Medical School
Sebastian Suerbaum: Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School
Siegfried Weiss: Helmholtz Centre for Infection Research
Immo Prinz: Institute of Immunology, Hannover Medical School

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7477

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