Adaptability of the semi‐invariant natural killer T‐cell receptor towards structurally diverse CD1d‐restricted ligands |
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| Authors: | Laura E Gordy Wenlan Chen Yalong Zhang James Scott‐Browne Yuki Kinjo Karl O A Yu Santosh Keshipeddy Daniel G Pellicci Onisha Patel Lars Kjer‐Nielsen James McCluskey Dale I Godfrey Jamie Rossjohn Stewart K Richardson Steven A Porcelli Amy R Howell Kyoko Hayakawa Laurent Gapin Dirk M Zajonc Peng George Wang Sebastian Joyce |
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| Institution: | 1. Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA;2. Department of Chemistry and Biochemistry, Ohio State University, Columbus, OH, USA;3. National Jewish Centre for Allergy and Immunology Research, Denver, CO, USA;4. Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA;5. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA;6. Department of Chemistry, University of Connecticut, Storrs, CT, USA;7. Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia;8. Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia;9. Fox Chase Cancer Centre, Philadelphia, PA, USA;10. Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA |
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| Abstract: | The semi‐invariant natural killer (NK) T‐cell receptor (NKTcr) recognises structurally diverse glycolipid antigens presented by the monomorphic CD1d molecule. While the α‐chain of the NKTcr is invariant, the β‐chain is more diverse, but how this diversity enables the NKTcr to recognise diverse antigens, such as an α‐linked monosaccharide (α‐galactosylceramide and α‐galactosyldiacylglycerol) and the β‐linked trisaccharide (isoglobotriaosylceramide), is unclear. We demonstrate here that NKTcrs, which varied in their β‐chain usage, recognised diverse glycolipid antigens with a similar binding mode on CD1d. Nevertheless, the NKTcrs recognised distinct epitopic sites within these antigens, including α‐galactosylceramide, the structurally similar α‐galactosyldiacylglycerol and the very distinct isoglobotriaosylceramide. We also show that the relative roles of the CDR loops within the NKTcr β‐chain varied as a function of the antigen. Thus, while NKTcrs characteristically use a conserved docking mode, the NKTcr β‐chain allows these cells to recognise unique aspects of structurally diverse CD1d‐restricted ligands. |
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| Keywords: | antigen recognition glycolipid antigens NKT cells recognition logic semi‐invariant T‐cell receptor |
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