Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens

Jérôme Le Nours; T Praveena; Daniel G Pellicci; Nicholas A Gherardin; Fiona J Ross; Ricky T Lim; Gurdyal S Besra; Santosh Keshipeddy; Stewart K Richardson; Amy R Howell; Stephanie Gras; Dale I Godfrey; Jamie Rossjohn; Adam P Uldrich

doi:10.1038/ncomms10570

Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens

Jérôme Le Nours, T Praveena, Daniel G Pellicci, Nicholas A Gherardin, Fiona J Ross, Ricky T Lim, Gurdyal S Besra, Santosh Keshipeddy, Stewart K Richardson, Amy R Howell, Stephanie Gras, Dale I Godfrey, Jamie Rossjohn, Adam P Uldrich

Biosciences

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex. However, the diversity of the NKT cell repertoire and the ensuing interactions with CD1d-antigen remain unclear. We describe an atypical population of CD1d-α-galactosylceramide (α-GalCer)-reactive human NKT cells that differ markedly from the prototypical TRAV10-TRAJ18-TRBV25-1(+) type I NKT cell repertoire. These cells express a range of TCR α- and β-chains that show differential recognition of glycolipid antigens. Two atypical NKT TCRs (TRAV21-TRAJ8-TRBV7-8 and TRAV12-3-TRAJ27-TRBV6-5) bind orthogonally over the A'-pocket of CD1d, adopting distinct docking modes that contrast with the docking mode of all type I NKT TCR-CD1d-antigen complexes. Moreover, the interactions with α-GalCer differ between the type I and these atypical NKT TCRs. Accordingly, diverse NKT TCR repertoire usage manifests in varied docking strategies and specificities towards CD1d-α-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition.

Original language	English
Article number	10570
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10570
Publication status	Published - 15 Feb 2016

Keywords

Biological sciences
Immunology
Molecular biology

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title = "Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens",

abstract = "Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex. However, the diversity of the NKT cell repertoire and the ensuing interactions with CD1d-antigen remain unclear. We describe an atypical population of CD1d-α-galactosylceramide (α-GalCer)-reactive human NKT cells that differ markedly from the prototypical TRAV10-TRAJ18-TRBV25-1(+) type I NKT cell repertoire. These cells express a range of TCR α- and β-chains that show differential recognition of glycolipid antigens. Two atypical NKT TCRs (TRAV21-TRAJ8-TRBV7-8 and TRAV12-3-TRAJ27-TRBV6-5) bind orthogonally over the A'-pocket of CD1d, adopting distinct docking modes that contrast with the docking mode of all type I NKT TCR-CD1d-antigen complexes. Moreover, the interactions with α-GalCer differ between the type I and these atypical NKT TCRs. Accordingly, diverse NKT TCR repertoire usage manifests in varied docking strategies and specificities towards CD1d-α-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition.",

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author = "{Le Nours}, J{\'e}r{\^o}me and T Praveena and Pellicci, {Daniel G} and Gherardin, {Nicholas A} and Ross, {Fiona J} and Lim, {Ricky T} and Besra, {Gurdyal S} and Santosh Keshipeddy and Richardson, {Stewart K} and Howell, {Amy R} and Stephanie Gras and Godfrey, {Dale I} and Jamie Rossjohn and Uldrich, {Adam P}",

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AU - Le Nours, Jérôme

AU - Praveena, T

AU - Pellicci, Daniel G

AU - Gherardin, Nicholas A

AU - Ross, Fiona J

AU - Lim, Ricky T

AU - Besra, Gurdyal S

AU - Keshipeddy, Santosh

AU - Richardson, Stewart K

AU - Howell, Amy R

AU - Gras, Stephanie

AU - Godfrey, Dale I

AU - Rossjohn, Jamie

AU - Uldrich, Adam P

PY - 2016/2/15

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N2 - Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex. However, the diversity of the NKT cell repertoire and the ensuing interactions with CD1d-antigen remain unclear. We describe an atypical population of CD1d-α-galactosylceramide (α-GalCer)-reactive human NKT cells that differ markedly from the prototypical TRAV10-TRAJ18-TRBV25-1(+) type I NKT cell repertoire. These cells express a range of TCR α- and β-chains that show differential recognition of glycolipid antigens. Two atypical NKT TCRs (TRAV21-TRAJ8-TRBV7-8 and TRAV12-3-TRAJ27-TRBV6-5) bind orthogonally over the A'-pocket of CD1d, adopting distinct docking modes that contrast with the docking mode of all type I NKT TCR-CD1d-antigen complexes. Moreover, the interactions with α-GalCer differ between the type I and these atypical NKT TCRs. Accordingly, diverse NKT TCR repertoire usage manifests in varied docking strategies and specificities towards CD1d-α-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition.

AB - Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex. However, the diversity of the NKT cell repertoire and the ensuing interactions with CD1d-antigen remain unclear. We describe an atypical population of CD1d-α-galactosylceramide (α-GalCer)-reactive human NKT cells that differ markedly from the prototypical TRAV10-TRAJ18-TRBV25-1(+) type I NKT cell repertoire. These cells express a range of TCR α- and β-chains that show differential recognition of glycolipid antigens. Two atypical NKT TCRs (TRAV21-TRAJ8-TRBV7-8 and TRAV12-3-TRAJ27-TRBV6-5) bind orthogonally over the A'-pocket of CD1d, adopting distinct docking modes that contrast with the docking mode of all type I NKT TCR-CD1d-antigen complexes. Moreover, the interactions with α-GalCer differ between the type I and these atypical NKT TCRs. Accordingly, diverse NKT TCR repertoire usage manifests in varied docking strategies and specificities towards CD1d-α-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition.

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KW - Immunology

KW - Molecular biology

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JO - Nature Communications

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Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens

Abstract

Keywords

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