Journal
NATURE IMMUNOLOGY
Volume 19, Issue 12, Pages 1352-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41590-018-0253-5
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Funding
- Francis Crick Institute from Cancer Research UK (CRUK) [FC001003]
- UK Medical Research Council [FC001003]
- Wellcome Trust [FC001003, 108745/Z/15/Z, 106292/Z/14/Z, 100156/Z/12/Z]
- CRUK King's Cancer Centre
- King's Bioscience Institute
- Guy's and St. Thomas' Charity Prize PhD program in Biomedical and Translational Science
- National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust
- King's College London
- St. Thomas' Wegener's Trust
- MRC [MR/P021964/1]
- Cluster of Excellence ExC 306 'Inflammationat-Interfaces'
- Cancer Research UK [23562]
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T lymphocytes expressing gamma delta T cell antigen receptors (TCRs) comprise evolutionarily conserved cells with paradoxical features. On the one hand, clonally expanded gamma delta T cells with unique specificities typify adaptive immunity. Conversely, large compartments of gamma delta TCR+ intraepithelial lymphocytes (gamma delta IELs) exhibit limited TCR diversity and effect rapid, innate-like tissue surveillance. The development of several gamma delta IEL compartments depends on epithelial expression of genes encoding butyrophilin-like (Btnl (mouse) or BTNL (human)) members of the B7 superfamily of T cell co-stimulators. Here we found that responsiveness to Btnl or BTNL proteins was mediated by germline-encoded motifs within the cognate TCR variable gamma-chains (V-gamma chains) of mouse and human gamma delta IELs. This was in contrast to diverse antigen recognition by clonally restricted complementarity-determining regions CDR1-CDR3 of the same gamma delta TCRs. Hence, the gamma delta TCR intrinsically combines innate immunity and adaptive immunity by using spatially distinct regions to discriminate non-clonal agonist-selecting elements from clone-specific ligands. The broader implications for antigen-receptor biology are considered.
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