Abstract
The clonal selection theory describes key features of adaptive immune responses of B and Tcells. For αβTcells and B cells, antigen recognition and selection principles are known at a detailed molecular level. The precise role of the antigen receptor in γδ Tcells remains less well understood. To better understand the role of the γδ Tcell receptor (TCR), we generate an orthotopic TCRδ transgenic mouse model. We demonstrate a multi-layered functionality of γδ TCRs and diverse roles of CDR3δ-mediated selection during γδTcell development. Whereas epithelial populations using Vγ5 or Vγ7 chains are almost unaffected in their biology in the presence of the transgenic TCRδ chain, pairing with Vγ1 positively selects γδ Tcell subpopulations 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.
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