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
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..View full abstract
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Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
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.