Journal
INTERNATIONAL IMMUNOLOGY
Volume 13, Issue 7, Pages 853-861Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/13.7.853
Keywords
alpha-galactosylceramide; NKT cell receptor; docking modeling
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A novel lymphocyte, NKT cells bearing an invariant V(alpha)14 antigen receptor, specifically recognizes alpha -galactosylceramide (alpha -GalCer) exclusively presented by mouse CD1d (mCD1d). However, the precise molecular interaction remains unclear. For the basis of functional analyses, a docking model of alpha -GalCer with the crystal structure of mCD1d was constructed. Possible residues involved in the alpha -GalCer-mCD1d interaction were found to be Arg79, Glu83 and Asp80 for carbohydrate recognition, and Asp153 for interaction with the amide group on the fatty acyl chain. The alpha -GaLCer-presenting ability of various transfectants expressing mutant mCD1d was completely abrogated it a single amino acid mutation was induced at positions 79, 80, 83 or 153, suggesting that the polar amino acids above the F ' pocket are crucial for alpha -GalCer presentation to activate V alpha 14 NKT cells. The possibility that Glu83 is a contact site for the NKT cell receptor is also discussed.
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