A monoclonal Trd chain supports the development of the complete set of functional γδ T cell lineages

The clonal selection theory describes the key features of adaptive immune responses of B and T cells. 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. 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.