CD1d protein structure determines species-selective antigenicity of isoglobotrihexosylceramide (iGb3) to invariant NKT cells

Joseph P Sanderson; Patrick J Brennan; Salah Mansour; Gediminas Matulis; Onisha Patel; Nikolai Lissin; Dale I Godfrey; Kazuyoshi Kawahara; Ulrich Zaehringer; Jamie Rossjohn; Michael B Brenner; Stephan D Gadola

Journal article

CD1d protein structure determines species-selective antigenicity of isoglobotrihexosylceramide (iGb3) to invariant NKT cells

Joseph P Sanderson, Patrick J Brennan, Salah Mansour, Gediminas Matulis, Onisha Patel, Nikolai Lissin, Dale I Godfrey, Kazuyoshi Kawahara, Ulrich Zaehringer, Jamie Rossjohn, Michael B Brenner, Stephan D Gadola

EUROPEAN JOURNAL OF IMMUNOLOGY | WILEY | Published : 2013

DOI: 10.1002/eji.201242952

Abstract

Isoglobotrihexosylceramide (iGb3) has been identified as a potent CD1d-presented self-antigen for mouse invariant natural killer T (iNKT) cells. The role of iGb3 in humans remains unresolved, however, as there have been conflicting reports about iGb3-dependent human iNKT-cell activation, and humans lack iGb3 synthase, a key enzyme for iGb3 synthesis. Given the importance of human immune responses, we conducted a human-mouse cross-species analysis of iNKT-cell activation by iGb3-CD1d. Here we show that human and mouse iNKT cells were both able to recognise iGb3 presented by mouse CD1d (mCD1d), but not human CD1d (hCD1d), as iGb3-hCD1d was unable to support cognate interactions with the iNKT-c..

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University of Melbourne Researchers

Dale Godfrey Author Microbiology and Immunology

Related Projects (3)

IMMUNE REGULATION EFFECTOR FUNCTION AND THERAPY

We seek to understand how white blood cells detect and destroy disease, and how molecules of the immune system punch holes in diseased cells..

Self-reactivity by NKT cells

NKT cells are a type of lymphocyte with the ability to prevent a broad range of diseases including cancer, autoimmunity, infection and graft..

IMMUNE REGULATION EFFECTOR FUNCTION AND THERAPY

We seek to understand how white blood cells detect and destroy disease, and how molecules of the immune system punch holes in diseased cells..

Grants

Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

Funding Acknowledgements

S.D.G, J.P.S and S. M. are supported by the Higher Education Funding Council for England (HEFCE). D. I. G. is supported by a National Health and Medical Research Council of Australia (NHMRC) Senior Principal Research Fellowship and J.R. is supported by an NHMRC Australia Fellowship.