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

• DOI: 10.1038/s41590-018-0253-5
• Publication Date: 2018-11-07T17:21:01Z
• Authors: Daisy Melandri; Iva Zlatareva; Raphaël A. G. Cha...; 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
• Keywords: 570; 0303 health sciences; Butyrophilins; 610; Receptors, Antigen, T-Cell, gamma-delta; Adaptive Immunity; Lymphocyte Activation; Immunity, Innate; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Animals; Humans; Antigens

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.