CD1d-lipid antigen recognition by the γδ TCR.
The T cell repertoire comprises αβ and γδ T cell lineages. Although it is established how αβ T cell antigen receptors (TCRs) interact with antigen presented by antigen-presenting molecules, this is unknown for γδ TCRs. We describe a population of human Vδ1(+) γδ T cells that exhibit autoreactivity to CD1d and provide a molecular basis for how a γδ TCR binds CD1d-α-galactosylceramide (α-GalCer). The γδ TCR docked orthogonally, over the A' pocket of CD1d, in which the Vδ1-chain, and in particular the germ line-encoded CDR1δ loop, dominated interactions with CD1d. The TCR γ-chain sat peripherally to the interface, with the CDR3γ loop representing the principal determinant for α-GalCer specificity. Accordingly, we provide insight into how a γδ TCR binds specifically to a lipid-loaded antigen-presenting molecule.
1] Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia. [2].
Adam P
AP
Uldrich
Jérôme
J
Le Nours
Daniel G
DG
Pellicci
Nicholas A
NA
Gherardin
Kirsty G
KG
McPherson
Ricky T
RT
Lim
Onisha
O
Patel
Travis
T
Beddoe
Stephanie
S
Gras
Jamie
J
Rossjohn
Dale I
DI
Godfrey
D000595:Amino Acid Sequence; D055610:Antigens, CD1d / Q000737:chemistry* / Q000276:immunology; D001665:Binding Sites; D030562:Databases, Protein; D005699:Galactosylceramides / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000737:chemistry* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D055610:Antigens, CD1d; C526877:CD1D protein, human; D005699:Galactosylceramides; D016692:Receptors, Antigen, T-Cell, gamma-delta; C493154:alpha-galactosylceramide