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


Natural killer T cells expressing 'invariant' T cell receptor alpha-chains (TCRalpha chains) containing variable (V) and joining (J) region Valpha14-Jalpha18 (Valpha14i) rearrangements recognize both endogenous and microbial glycolipids in the context of CD1d. How cells expressing an invariant TCRalpha chain and a restricted set of TCRbeta chains recognize structurally diverse antigens is not clear. Here we show that a Valpha14i TCR recognized many alpha-linked glycolipids by means of a 'hot-spot' of germline-encoded amino acids in complementarity-determining regions 3alpha, 1alpha and 2beta. This hot-spot did not shift during the recognition of structurally distinct antigens, suggesting that the Valpha14i 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 alpha-linked glycolipids.

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  1. Department of Immunology, University of Colorado Health Sciences Center and National Jewish Medical and Research Center, Denver, Colorado, 80206, USA.
  2. 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.
  3. Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
  4. Howard Hughes Medical Institute and University of Colorado Health Sciences Center, Denver, Colorado 80220, USA.
  5. Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Ist 80220, USA.
  6. Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80220, USA.
  7. Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, Colorado 80220, USA.
  8. These authors contributed equally to this work.

Correspondence to: Laurent Gapin1 e-mail: gapinl@njc.org

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