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

New article on Cell Reports in March 2023

The clonal selection theory describes key features of adaptive immune responses of B and T cells. For ab 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 gd T cells remains less well understood. To better understand the role of the gd T cell receptor (TCR), we generate an orthotopic TCRd transgenic mouse model. We demonstrate a multi-layered functionality of gd TCRs and diverse roles of CDR3d-mediated selection during gd T cell development. Whereas epithelial populations using Vg5 or Vg7 chains are almost unaffected in their biology in the presence of the transgenic TCRd chain, pairing with Vg1 positively selects gd T cell 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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