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Publication Abstract from PubMed

Invariant natural killer T cells (iNKT cells) rapidly produce effector cytokines. In this study, we report the first crystal structures of the iNKT cell T cell receptor (TCR) bound to two natural, microbial glycolipids presented by CD1d. Binding of the TCR induced CDR3-alpha-dependent structural changes in the F' roof of CD1d; these changes resemble those occurring in the absence of TCR engagement when the highly potent synthetic antigen alpha-galactosylceramide (alpha-GalCer) binds CD1d. Furthermore, in the Borrelia burgdorferi alpha-galactosyl diacylglycerol-CD1d complex, TCR binding caused a marked repositioning of the galactose sugar into an orientation that closely resembles alpha-GalCer. The TCR-dependent reorientation of the sugar, together with the induced CD1d fit, may explain the weaker potency of the microbial antigens compared with alpha-GalCer. We propose that the TCR of iNKT cells binds with a conserved footprint onto CD1d, regardless of the bound glycolipid antigen, and that for microbial antigens this unique binding mode requires TCR-initiated conformational changes.

The V{alpha}14 invariant natural killer T cell TCR forces microbial glycolipids and CD1d into a conserved binding mode.,Li Y, Girardi E, Wang J, Yu ED, Painter GF, Kronenberg M, Zajonc DM J Exp Med. 2010 Oct 4. PMID:20921281^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.