CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor

Natalie Borg, Kwok Soon Wun, Lars Kjer-Nielsen, Matthew Charles James Wilce, Daniel G Pellicci, Ruide Koh, Gurdyal S Besra, Mandvi Bharadwaj, Dale I Godfrey, James McCluskey, Jamie Rossjohn

Research output: Contribution to journalArticleResearchpeer-review

426 Citations (Scopus)

Abstract

The CD1 family is a large cluster of non-polymorphic, major histocompatibility complex (MHC) class-I-like molecules that bind distinct lipid-based antigens that are recognized by T cells. The most studied group of T cells that interact with lipid antigens are natural killer T (NKT) cells, which characteristically express a semi-invariant T-cell receptor (NKT TCR) that specifically recognizes the CD1 family member, CD1d. NKT-cell-mediated recognition of the CD1d?antigen complex has been implicated in microbial immunity, tumour immunity, autoimmunity and allergy. Here we describe the structure of a human NKT TCR in complex with CD1d bound to the potent NKT-cell agonist -galactosylceramide, the archetypal CD1d-restricted glycolipid. In contrast to T-cell receptor?peptide-antigen?MHC complexes, the NKT TCR docked parallel to, and at the extreme end of the CD1d-binding cleft, which enables a lock-and-key type interaction with the lipid antigen. The structure provides a basis for the interaction between the highly conserved NKT TCR -chain and the CD1d?antigen complex that is typified in innate immunity, and also indicates how variability of the NKT TCR -chain can impact on recognition of other CD1d?antigen complexes. These findings provide direct insight into how a T-cell receptor recognizes a lipid-antigen-presenting molecule of the immune system.
Original languageEnglish
Pages (from-to)44 - 49
Number of pages6
JournalNature
Volume448
Issue number7149
Publication statusPublished - 2007

Cite this

Borg, N., Wun, K. S., Kjer-Nielsen, L., Wilce, M. C. J., Pellicci, D. G., Koh, R., ... Rossjohn, J. (2007). CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature, 448(7149), 44 - 49.
Borg, Natalie ; Wun, Kwok Soon ; Kjer-Nielsen, Lars ; Wilce, Matthew Charles James ; Pellicci, Daniel G ; Koh, Ruide ; Besra, Gurdyal S ; Bharadwaj, Mandvi ; Godfrey, Dale I ; McCluskey, James ; Rossjohn, Jamie. / CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. In: Nature. 2007 ; Vol. 448, No. 7149. pp. 44 - 49.
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abstract = "The CD1 family is a large cluster of non-polymorphic, major histocompatibility complex (MHC) class-I-like molecules that bind distinct lipid-based antigens that are recognized by T cells. The most studied group of T cells that interact with lipid antigens are natural killer T (NKT) cells, which characteristically express a semi-invariant T-cell receptor (NKT TCR) that specifically recognizes the CD1 family member, CD1d. NKT-cell-mediated recognition of the CD1d?antigen complex has been implicated in microbial immunity, tumour immunity, autoimmunity and allergy. Here we describe the structure of a human NKT TCR in complex with CD1d bound to the potent NKT-cell agonist -galactosylceramide, the archetypal CD1d-restricted glycolipid. In contrast to T-cell receptor?peptide-antigen?MHC complexes, the NKT TCR docked parallel to, and at the extreme end of the CD1d-binding cleft, which enables a lock-and-key type interaction with the lipid antigen. The structure provides a basis for the interaction between the highly conserved NKT TCR -chain and the CD1d?antigen complex that is typified in innate immunity, and also indicates how variability of the NKT TCR -chain can impact on recognition of other CD1d?antigen complexes. These findings provide direct insight into how a T-cell receptor recognizes a lipid-antigen-presenting molecule of the immune system.",
author = "Natalie Borg and Wun, {Kwok Soon} and Lars Kjer-Nielsen and Wilce, {Matthew Charles James} and Pellicci, {Daniel G} and Ruide Koh and Besra, {Gurdyal S} and Mandvi Bharadwaj and Godfrey, {Dale I} and James McCluskey and Jamie Rossjohn",
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Borg, N, Wun, KS, Kjer-Nielsen, L, Wilce, MCJ, Pellicci, DG, Koh, R, Besra, GS, Bharadwaj, M, Godfrey, DI, McCluskey, J & Rossjohn, J 2007, 'CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor', Nature, vol. 448, no. 7149, pp. 44 - 49.

CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. / Borg, Natalie; Wun, Kwok Soon; Kjer-Nielsen, Lars; Wilce, Matthew Charles James; Pellicci, Daniel G; Koh, Ruide; Besra, Gurdyal S; Bharadwaj, Mandvi; Godfrey, Dale I; McCluskey, James; Rossjohn, Jamie.

In: Nature, Vol. 448, No. 7149, 2007, p. 44 - 49.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Borg, Natalie

AU - Wun, Kwok Soon

AU - Kjer-Nielsen, Lars

AU - Wilce, Matthew Charles James

AU - Pellicci, Daniel G

AU - Koh, Ruide

AU - Besra, Gurdyal S

AU - Bharadwaj, Mandvi

AU - Godfrey, Dale I

AU - McCluskey, James

AU - Rossjohn, Jamie

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N2 - The CD1 family is a large cluster of non-polymorphic, major histocompatibility complex (MHC) class-I-like molecules that bind distinct lipid-based antigens that are recognized by T cells. The most studied group of T cells that interact with lipid antigens are natural killer T (NKT) cells, which characteristically express a semi-invariant T-cell receptor (NKT TCR) that specifically recognizes the CD1 family member, CD1d. NKT-cell-mediated recognition of the CD1d?antigen complex has been implicated in microbial immunity, tumour immunity, autoimmunity and allergy. Here we describe the structure of a human NKT TCR in complex with CD1d bound to the potent NKT-cell agonist -galactosylceramide, the archetypal CD1d-restricted glycolipid. In contrast to T-cell receptor?peptide-antigen?MHC complexes, the NKT TCR docked parallel to, and at the extreme end of the CD1d-binding cleft, which enables a lock-and-key type interaction with the lipid antigen. The structure provides a basis for the interaction between the highly conserved NKT TCR -chain and the CD1d?antigen complex that is typified in innate immunity, and also indicates how variability of the NKT TCR -chain can impact on recognition of other CD1d?antigen complexes. These findings provide direct insight into how a T-cell receptor recognizes a lipid-antigen-presenting molecule of the immune system.

AB - The CD1 family is a large cluster of non-polymorphic, major histocompatibility complex (MHC) class-I-like molecules that bind distinct lipid-based antigens that are recognized by T cells. The most studied group of T cells that interact with lipid antigens are natural killer T (NKT) cells, which characteristically express a semi-invariant T-cell receptor (NKT TCR) that specifically recognizes the CD1 family member, CD1d. NKT-cell-mediated recognition of the CD1d?antigen complex has been implicated in microbial immunity, tumour immunity, autoimmunity and allergy. Here we describe the structure of a human NKT TCR in complex with CD1d bound to the potent NKT-cell agonist -galactosylceramide, the archetypal CD1d-restricted glycolipid. In contrast to T-cell receptor?peptide-antigen?MHC complexes, the NKT TCR docked parallel to, and at the extreme end of the CD1d-binding cleft, which enables a lock-and-key type interaction with the lipid antigen. The structure provides a basis for the interaction between the highly conserved NKT TCR -chain and the CD1d?antigen complex that is typified in innate immunity, and also indicates how variability of the NKT TCR -chain can impact on recognition of other CD1d?antigen complexes. These findings provide direct insight into how a T-cell receptor recognizes a lipid-antigen-presenting molecule of the immune system.

UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17581592

M3 - Article

VL - 448

SP - 44

EP - 49

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7149

ER -

Borg N, Wun KS, Kjer-Nielsen L, Wilce MCJ, Pellicci DG, Koh R et al. CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature. 2007;448(7149):44 - 49.