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

Cell Rep. 2023 Mar 28;42(3):112253. doi: 10.1016/j.celrep.2023.112253. Epub 2023 Mar 14.

Abstract

The clonal selection theory describes 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), 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 γδ T cell 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 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.

Keywords: CP: Immunology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage
  • Intraepithelial Lymphocytes*
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, gamma-delta*

Substances

  • Receptors, Antigen, T-Cell, gamma-delta