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For αβ T cells and B cells antigen recognition and selection principles are known at a detailed molecular level. The precise role of the antigen receptor in γδ T cells remains less well understood. To better understand the role of the γδ T cell receptor (TCR), in particular its specificity for thymic selection of γδ T cells and for γδ T cell biology in general, we generated a novel orthotopic TCRδ transgenic mouse model. We demonstrate a multi-layered functionality of γδ TCRs and diverse roles of CDR3δ-mediated selection during γδ T cell development. Whereas epithelial populations using Vγ5 or Vγ7 chains are affected to only minor extend in their biology in the presence of a single TCRδ chain, pairing with Vγ1 positively selects subpopulations of γδ T cells with distinct programs in several organs, thereby distorting the repertoire. In conclusion, our data support dictation of developmental tropism together with adaptive-like recognition principles in a single antigen receptor. Overall design: Murine γδ T cells were isolated from the spleen via Fluorescence-activated cell sorting (FACS) according to the presence of CD3 and γδTCR and the absence of αβTCR, B220 and CD11c, and analyzed using scRNAseq for transcriptome and V(D)J repertoire analysis.</long_description><repository>ENA</repository></additional><is_claimable>false</is_claimable><name>A monoclonal Trd chain supports the development of the complete set of functional γδ T cell lineages (GEX)</name><description>A monoclonal Trd chain supports the development of the complete set of functional γδ T cell lineages (GEX)</description><dates><last_updated>2025-09-24</last_updated><first_public>2023-03-06</first_public></dates><accession>PRJNA934585</accession><cross_references><GEO>GSE225032</GEO><taxon>10090</taxon><PubMed>37182210</PubMed></cross_references></HashMap>