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

Jerome Le Nours, Thirunavukkarasu 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

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16 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-alpha-galactosylceramide (alpha-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 alpha- and beta-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 alpha-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-alpha-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition.
Original languageEnglish
Article number10570
Number of pages14
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 2016

Cite this

Le Nours, J., Praveena, T., Pellicci, D. G., Gherardin, N. A., Ross, F. J., Lim, R. T., ... Uldrich, A. P. (2016). Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens. Nature Communications, 7, [10570]. https://doi.org/10.1038/ncomms10570
Le Nours, Jerome ; Praveena, Thirunavukkarasu ; Pellicci, Daniel G ; Gherardin, Nicholas A ; Ross, Fiona J ; Lim, Ricky T ; Besra, Gurdyal S ; Keshipeddy, Santosh ; Richardson, Stewart K ; Howell, Amy R ; Gras, Stephanie ; Godfrey, Dale I ; Rossjohn, Jamie ; Uldrich, Adam P. / Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens. In: Nature Communications. 2016 ; Vol. 7.
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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-alpha-galactosylceramide (alpha-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 alpha- and beta-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 alpha-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-alpha-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition.",
author = "{Le Nours}, Jerome and Thirunavukkarasu 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}",
year = "2016",
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Le Nours, J, Praveena, T, Pellicci, DG, Gherardin, NA, Ross, FJ, Lim, RT, Besra, GS, Keshipeddy, S, Richardson, SK, Howell, AR, Gras, S, Godfrey, DI, Rossjohn, J & Uldrich, AP 2016, 'Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens', Nature Communications, vol. 7, 10570. https://doi.org/10.1038/ncomms10570

Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens. / Le Nours, Jerome; Praveena, Thirunavukkarasu; Pellicci, Daniel G; Gherardin, Nicholas A; Ross, Fiona J; Lim, Ricky T; Besra, Gurdyal S; Keshipeddy, Santosh; Richardson, Stewart K; Howell, Amy R; Gras, Stephanie; Godfrey, Dale I; Rossjohn, Jamie; Uldrich, Adam P.

In: Nature Communications, Vol. 7, 10570, 2016.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens

AU - Le Nours, Jerome

AU - Praveena, Thirunavukkarasu

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

Y1 - 2016

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-alpha-galactosylceramide (alpha-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 alpha- and beta-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 alpha-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-alpha-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-alpha-galactosylceramide (alpha-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 alpha- and beta-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 alpha-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-alpha-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition.

UR - http://www.ncbi.nlm.nih.gov/pubmed/26875526

U2 - 10.1038/ncomms10570

DO - 10.1038/ncomms10570

M3 - Article

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 10570

ER -