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The γδTCR combines innate immunity with adaptive immunity by utilizing spatially distinct regions for agonist selection and antigen responsiveness

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Daisy Melandri, Iva Zlatareva, Raphaël A.G. Chaleil, Robin J. Dart, Andrew Chancellor, Oliver Nussbaumer, Oxana Polyakova, Natalie A. Roberts, Daniela Wesch, Dieter Kabelitz, Peter M. Irving, Susan John, Salah Mansour, Paul A. Bates, Pierre Vantourout, Adrian C. Hayday

Original languageEnglish
Pages (from-to)1352-1365
Number of pages14
JournalNature Immunology
Volume19
Issue number12
Early online date12 Nov 2018
DOIs
Accepted/In press8 Oct 2018
E-pub ahead of print12 Nov 2018
Published1 Dec 2018

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Abstract

T lymphocytes expressing γδ T cell antigen receptors (TCRs) comprise evolutionarily conserved cells with paradoxical features. On the one hand, clonally expanded γδ T cells with unique specificities typify adaptive immunity. Conversely, large compartments of γδTCR+ intraepithelial lymphocytes (γδ IELs) exhibit limited TCR diversity and effect rapid, innate-like tissue surveillance. The development of several γδ 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 γ-chains (Vγ chains) of mouse and human γδ IELs. This was in contrast to diverse antigen recognition by clonally restricted complementarity-determining regions CDR1–CDR3 of the same γδTCRs. Hence, the γδTCR 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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