J Exp Med. 2010 Oct 25;207(11):2383-93. Epub 2010 Oct 4.

The Vα14 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.

Source

Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.

Abstract

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-α-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 α-galactosylceramide (α-GalCer) binds CD1d. Furthermore, in the Borrelia burgdorferi α-galactosyl diacylglycerol-CD1d complex, TCR binding caused a marked repositioning of the galactose sugar into an orientation that closely resembles α-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 α-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.