Article abstract
Nature Immunology 8, 1105 - 1113 (2007)
Published online: 9 September 2007 | doi:10.1038/ni1510
Germline-encoded recognition of diverse glycolipids by natural killer T cells
James P Scott-Browne1,8, Jennifer L Matsuda1,8, Thierry Mallevaey1, Janice White1, Natalie A Borg2, James McCluskey3, Jamie Rossjohn2, John Kappler1,4,5,6, Philippa Marrack1,4,6,7 & Laurent Gapin1
Abstract
Natural killer T cells expressing 'invariant' T cell receptor
-chains (TCR
chains) containing variable (V) and joining (J) region V
14-J
18 (V
14i) rearrangements recognize both endogenous and microbial glycolipids in the context of CD1d. How cells expressing an invariant TCR
chain and a restricted set of TCR
chains recognize structurally diverse antigens is not clear. Here we show that a V
14i TCR recognized many
-linked glycolipids by means of a 'hot-spot' of germline-encoded amino acids in complementarity-determining regions 3
, 1
and 2
. This hot-spot did not shift during the recognition of structurally distinct antigens, suggesting that the V
14i TCR functions as a pattern-recognition receptor, conferring on natural killer T cells the ability to sense and respond in an innate way to pathogens displaying antigenic
-linked glycolipids.
- Department of Immunology, University of Colorado Health Sciences Center and National Jewish Medical and Research Center, Denver, Colorado, 80206, USA.
- The Protein Crystallography Unit, ARC Centre of Excellence in Structural and Functional Microbial Genomics, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
- Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
- Howard Hughes Medical Institute and University of Colorado Health Sciences Center, Denver, Colorado 80220, USA.
- Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Ist 80220, USA.
- Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80220, USA.
- Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, Colorado 80220, USA.
- These authors contributed equally to this work.
Correspondence to: Laurent Gapin1 e-mail: gapinl@njc.org
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