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

TY - JOUR

T1 - The γδTCR combines innate immunity with adaptive immunity by utilizing spatially distinct regions for agonist selection and antigen responsiveness

AU - Melandri, Daisy

AU - Zlatareva, Iva

AU - Chaleil, Raphaël A.G.

AU - Dart, Robin J.

AU - Chancellor, Andrew

AU - Nussbaumer, Oliver

AU - Polyakova, Oxana

AU - Roberts, Natalie A.

AU - Wesch, Daniela

AU - Kabelitz, Dieter

AU - Irving, Peter M.

AU - John, Susan

AU - Mansour, Salah

AU - Bates, Paul A.

AU - Vantourout, Pierre

AU - Hayday, Adrian C.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85056453042&partnerID=8YFLogxK

U2 - 10.1038/s41590-018-0253-5

DO - 10.1038/s41590-018-0253-5

M3 - Article

C2 - 30420626

AN - SCOPUS:85056453042

SN - 1529-2908

VL - 19

SP - 1352

EP - 1365

JO - Nature Immunology

JF - Nature Immunology

IS - 12

ER -