Structural Basis for CD1d Presentation of a Sulfatide Derived from Myelin and Its Implications for Autoimmunity

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2005 Nov 30

PMID 16314439

Citations 107

Authors

Dirk M Zajonc

Igor Maricic

Douglass Wu

Ramesh Halder

Keshab Roy

Chi-Huey Wong

Vipin Kumar

Ian A Wilson

Affiliations

Soon will be listed here.

Abstract

Sulfatide derived from the myelin stimulates a distinct population of CD1d-restricted natural killer T (NKT) cells. Cis-tetracosenoyl sulfatide is one of the immunodominant species in myelin as identified by proliferation, cytokine secretion, and CD1d tetramer staining. The crystal structure of mouse CD1d in complex with cis-tetracosenoyl sulfatide at 1.9 A resolution reveals that the longer cis-tetracosenoyl fatty acid chain fully occupies the A' pocket of the CD1d binding groove, whereas the sphingosine chain fills up the F' pocket. A precise hydrogen bond network in the center of the binding groove orients and positions the ceramide backbone for insertion of the lipid tails in their respective pockets. The 3'-sulfated galactose headgroup is highly exposed for presentation to the T cell receptor and projects up and away from the binding pocket due to its beta linkage, compared with the more intimate binding of the alpha-glactosyl ceramide headgroup to CD1d. These structure and binding data on sulfatide presentation by CD1d have important implications for the design of therapeutics that target T cells reactive for myelin glycolipids in autoimmune diseases of the central nervous system.

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References

Batuwangala T, Shepherd D, Gadola S, Gibson K, Zaccai N, Fersht A . The crystal structure of human CD1b with a bound bacterial glycolipid. J Immunol. 2004; 172(4):2382-8. DOI: 10.4049/jimmunol.172.4.2382. View

Wu D, Segal N, Sidobre S, Kronenberg M, Chapman P . Cross-presentation of disialoganglioside GD3 to natural killer T cells. J Exp Med. 2003; 198(1):173-81. PMC: 2196074. DOI: 10.1084/jem.20030446. View

Brigl M, Brenner M . CD1: antigen presentation and T cell function. Annu Rev Immunol. 2004; 22:817-90. DOI: 10.1146/annurev.immunol.22.012703.104608. View

Nicholls A, Sharp K, Honig B . Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins. 1991; 11(4):281-96. DOI: 10.1002/prot.340110407. View

Jahng A, Maricic I, Aguilera C, Cardell S, Halder R, Kumar V . Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide. J Exp Med. 2004; 199(7):947-57. PMC: 2211873. DOI: 10.1084/jem.20031389. View

Winn M, Isupov M, Murshudov G . Use of TLS parameters to model anisotropic displacements in macromolecular refinement. Acta Crystallogr D Biol Crystallogr. 2001; 57(Pt 1):122-33. DOI: 10.1107/s0907444900014736. View

Jones T, Zou J, Cowan S, Kjeldgaard M . Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A. 1991; 47 ( Pt 2):110-9. DOI: 10.1107/s0108767390010224. View

De Libero G, Mori L . Recognition of lipid antigens by T cells. Nat Rev Immunol. 2005; 5(6):485-96. DOI: 10.1038/nri1631. View

Wilson S, Delovitch T . Janus-like role of regulatory iNKT cells in autoimmune disease and tumour immunity. Nat Rev Immunol. 2003; 3(3):211-22. DOI: 10.1038/nri1028. View

10.

Wu D, Xing G, Poles M, Horowitz A, Kinjo Y, Sullivan B . Bacterial glycolipids and analogs as antigens for CD1d-restricted NKT cells. Proc Natl Acad Sci U S A. 2005; 102(5):1351-6. PMC: 547854. DOI: 10.1073/pnas.0408696102. View

11.

Giabbai B, Sidobre S, Crispin M, Sanchez-Ruiz Y, Bachi A, Kronenberg M . Crystal structure of mouse CD1d bound to the self ligand phosphatidylcholine: a molecular basis for NKT cell activation. J Immunol. 2005; 175(2):977-84. DOI: 10.4049/jimmunol.175.2.977. View

12.

Acarin N, Rio J, Fernandez A, Tintore M, Duran I, Galan I . Different antiganglioside antibody pattern between relapsing-remitting and progressive multiple sclerosis. Acta Neurol Scand. 1996; 93(2-3):99-103. DOI: 10.1111/j.1600-0404.1996.tb00182.x. View

13.

Zhou D, Cantu 3rd C, Sagiv Y, Schrantz N, Kulkarni A, Qi X . Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins. Science. 2003; 303(5657):523-7. PMC: 2918537. DOI: 10.1126/science.1092009. View

14.

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

15.

Stevens A, Weller M, Wietholter H . CSF and serum ganglioside antibody patterns in MS. Acta Neurol Scand. 1992; 86(5):485-9. DOI: 10.1111/j.1600-0404.1992.tb05129.x. View

16.

Jahng A, Maricic I, Pedersen B, Burdin N, Naidenko O, Kronenberg M . Activation of natural killer T cells potentiates or prevents experimental autoimmune encephalomyelitis. J Exp Med. 2001; 194(12):1789-99. PMC: 2193586. DOI: 10.1084/jem.194.12.1789. View

17.

Murshudov G, Vagin A, Dodson E . Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr D Biol Crystallogr. 1997; 53(Pt 3):240-55. DOI: 10.1107/S0907444996012255. View

18.

Kolter T, Sandhoff K . Principles of lysosomal membrane digestion: stimulation of sphingolipid degradation by sphingolipid activator proteins and anionic lysosomal lipids. Annu Rev Cell Dev Biol. 2005; 21:81-103. DOI: 10.1146/annurev.cellbio.21.122303.120013. View

19.

Lubetzki C, THUILLIER Y, Galli A, Lyon-Caen O, LHERMITTE F, Zalc B . Galactosylceramide: a reliable serum index of demyelination in multiple sclerosis. Ann Neurol. 1989; 26(3):407-9. DOI: 10.1002/ana.410260319. View

20.

Godfrey D, McCluskey J, Rossjohn J . CD1d antigen presentation: treats for NKT cells. Nat Immunol. 2005; 6(8):754-6. DOI: 10.1038/ni0805-754. View