A Semi-invariant Vα10+ T Cell Antigen Receptor Defines a Population of Natural Killer T Cells with Distinct Glycolipid Antigen-recognition Properties

Overview

Journal Nat Immunol

Date 2011 Jun 14

PMID 21666690

Citations 68

Authors

Adam P Uldrich

Onisha Patel

Garth Cameron

Daniel G Pellicci

E Bridie Day

Lucy C Sullivan

Konstantinos Kyparissoudis

Lars Kjer-Nielsen

Julian P Vivian

Benjamin Cao

Andrew G Brooks

Spencer J Williams

Petr Illarionov

Gurdyal S Besra

Stephen J Turner

Steven A Porcelli

James McCluskey

Mark J Smyth

Jamie Rossjohn

Dale I Godfrey

Affiliations

Soon will be listed here.

Abstract

Type I natural killer T cells (NKT cells) are characterized by an invariant variable region 14-joining region 18 (V(α)14-J(α)18) T cell antigen receptor (TCR) α-chain and recognition of the glycolipid α-galactosylceramide (α-GalCer) restricted to the antigen-presenting molecule CD1d. Here we describe a population of α-GalCer-reactive NKT cells that expressed a canonical V(α)10-J(α)50 TCR α-chain, which showed a preference for α-glucosylceramide (α-GlcCer) and bacterial α-glucuronic acid-containing glycolipid antigens. Structurally, despite very limited TCRα sequence identity, the V(α)10 TCR-CD1d-α-GlcCer complex had a docking mode similar to that of type I TCR-CD1d-α-GalCer complexes, although differences at the antigen-binding interface accounted for the altered antigen specificity. Our findings provide new insight into the structural basis and evolution of glycolipid antigen recognition and have notable implications for the scope and immunological role of glycolipid-specific T cell responses.

Citing Articles

Lipidomic scanning of self-lipids identifies headless antigens for natural killer T cells.

Cheng T, Praveena T, Govindarajan S, Almeida C, Pellicci D, Arkins W Proc Natl Acad Sci U S A. 2024; 121(34):e2321686121.

PMID: 39141352 PMC: 11348285. DOI: 10.1073/pnas.2321686121.

A structural perspective of how T cell receptors recognize the CD1 family of lipid antigen-presenting molecules.

Cao T, Shahine A, Cox L, Besra G, Moody D, Rossjohn J J Biol Chem. 2024; 300(8):107511.

PMID: 38945451 PMC: 11780374. DOI: 10.1016/j.jbc.2024.107511.

CAR products from novel sources: a new avenue for the breakthrough in cancer immunotherapy.

Huang J, Yang Q, Wang W, Huang J Front Immunol. 2024; 15:1378739.

PMID: 38665921 PMC: 11044028. DOI: 10.3389/fimmu.2024.1378739.

MAITs and their mates: "Innate-like" behaviors in conventional and unconventional T cells.

Hackstein C, Klenerman P Clin Exp Immunol. 2023; 213(1):1-9.

PMID: 37256718 PMC: 10324555. DOI: 10.1093/cei/uxad058.

Pathogenic NKT cells attenuate urogenital chlamydial clearance and enhance infertility.

Armitage C, Carey A, Bryan E, Kollipara A, Trim L, Beagley K Scand J Immunol. 2023; 97(5):e13263.

PMID: 36872855 PMC: 10909442. DOI: 10.1111/sji.13263.

References

. The CCP4 suite: programs for protein crystallography. Acta Crystallogr D Biol Crystallogr. 1994; 50(Pt 5):760-3. DOI: 10.1107/S0907444994003112. View

Feng D, Bond C, Ely L, Maynard J, Garcia K . Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'. Nat Immunol. 2007; 8(9):975-83. DOI: 10.1038/ni1502. View

Scott-Browne J, Matsuda J, Mallevaey T, White J, Borg N, McCluskey J . Germline-encoded recognition of diverse glycolipids by natural killer T cells. Nat Immunol. 2007; 8(10):1105-13. DOI: 10.1038/ni1510. View

Day E, Zeng W, Doherty P, Jackson D, Kedzierska K, Turner S . The context of epitope presentation can influence functional quality of recalled influenza A virus-specific memory CD8+ T cells. J Immunol. 2007; 179(4):2187-94. DOI: 10.4049/jimmunol.179.4.2187. View

Wun K, Cameron G, Patel O, Pang S, Pellicci D, Sullivan L . A molecular basis for the exquisite CD1d-restricted antigen specificity and functional responses of natural killer T cells. Immunity. 2011; 34(3):327-39. PMC: 3064745. DOI: 10.1016/j.immuni.2011.02.001. View

Kim J, Choi E, Chung D . Donor bone marrow type II (non-Valpha14Jalpha18 CD1d-restricted) NKT cells suppress graft-versus-host disease by producing IFN-gamma and IL-4. J Immunol. 2007; 179(10):6579-87. DOI: 10.4049/jimmunol.179.10.6579. View

Jervis P, Veerapen N, Bricard G, Cox L, Porcelli S, Besra G . Synthesis and biological activity of alpha-glucosyl C24:0 and C20:2 ceramides. Bioorg Med Chem Lett. 2010; 20(12):3475-8. PMC: 4374101. DOI: 10.1016/j.bmcl.2010.05.010. View

Stenstrom M, Skold M, Andersson A, Cardell S . Natural killer T-cell populations in C57BL/6 and NK1.1 congenic BALB.NK mice-a novel thymic subset defined in BALB.NK mice. Immunology. 2005; 114(3):336-45. PMC: 1782094. DOI: 10.1111/j.1365-2567.2004.02111.x. View

Kawano T, Cui J, Koezuka Y, Toura I, Kaneko Y, Motoki K . CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science. 1997; 278(5343):1626-9. DOI: 10.1126/science.278.5343.1626. View

10.

Long X, Deng S, Mattner J, Zang Z, Zhou D, McNary N . Synthesis and evaluation of stimulatory properties of Sphingomonadaceae glycolipids. Nat Chem Biol. 2007; 3(9):559-64. DOI: 10.1038/nchembio.2007.19. View

11.

Gadola S, Dulphy N, Salio M, Cerundolo V . Valpha24-JalphaQ-independent, CD1d-restricted recognition of alpha-galactosylceramide by human CD4(+) and CD8alphabeta(+) T lymphocytes. J Immunol. 2002; 168(11):5514-20. DOI: 10.4049/jimmunol.168.11.5514. View

12.

Dai S, Huseby E, Rubtsova K, Scott-Browne J, Crawford F, Macdonald W . Crossreactive T Cells spotlight the germline rules for alphabeta T cell-receptor interactions with MHC molecules. Immunity. 2008; 28(3):324-34. PMC: 2287197. DOI: 10.1016/j.immuni.2008.01.008. View

13.

Terabe M, Swann J, Ambrosino E, Sinha P, Takaku S, Hayakawa Y . A nonclassical non-Valpha14Jalpha18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance. J Exp Med. 2005; 202(12):1627-33. PMC: 2212961. DOI: 10.1084/jem.20051381. View

14.

Borg N, Wun K, Kjer-Nielsen L, Wilce M, Pellicci D, Koh R . CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature. 2007; 448(7149):44-9. DOI: 10.1038/nature05907. View

15.

Kedzierska K, Turner S, Doherty P . Conserved T cell receptor usage in primary and recall responses to an immunodominant influenza virus nucleoprotein epitope. Proc Natl Acad Sci U S A. 2004; 101(14):4942-7. PMC: 387353. DOI: 10.1073/pnas.0401279101. View

16.

Garboczi D, Utz U, Ghosh P, Seth A, Kim J, VanTienhoven E . Assembly, specific binding, and crystallization of a human TCR-alphabeta with an antigenic Tax peptide from human T lymphotropic virus type 1 and the class I MHC molecule HLA-A2. J Immunol. 1996; 157(12):5403-10. View

17.

Kjer-Nielsen L, Borg N, Pellicci D, Beddoe T, Kostenko L, Clements C . A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition. J Exp Med. 2006; 203(3):661-73. PMC: 2118261. DOI: 10.1084/jem.20051777. View

18.

Renukaradhya G, Khan M, Vieira M, Du W, Gervay-Hague J, Brutkiewicz R . Type I NKT cells protect (and type II NKT cells suppress) the host's innate antitumor immune response to a B-cell lymphoma. Blood. 2008; 111(12):5637-45. PMC: 2424159. DOI: 10.1182/blood-2007-05-092866. View

19.

Crowe N, Coquet J, Berzins S, Kyparissoudis K, Keating R, Pellicci D . Differential antitumor immunity mediated by NKT cell subsets in vivo. J Exp Med. 2005; 202(9):1279-88. PMC: 1459911. DOI: 10.1084/jem.20050953. View

20.

Blomqvist M, Rhost S, Teneberg S, Lofbom L, Osterbye T, Brigl M . Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells. Eur J Immunol. 2009; 39(7):1726-35. PMC: 4212524. DOI: 10.1002/eji.200839001. View