Published in

National Academy of Sciences, Proceedings of the National Academy of Sciences, 9(113), 2016

DOI: 10.1073/pnas.1519246113

Links

Tools

Export citation

Search in Google Scholar

Cholesteryl esters stabilize human CD1c conformations for recognition by self-reactive T cells

Journal article published in 2016 by Salah Mansour ORCID, Anna S. Tocheva, Chris Cave-Ayland, Moritz M. Machelett ORCID, Barbara Sander, Nikolai M. Lissin, Peter E. Molloy, Mark S. Baird ORCID, Gunthard Stübs, Nicolas W. J. Schröder, Ralf R. Schumann, Jörg Rademann ORCID, Anthony D. Postle, Bent K. Jakobsen, Ben G. Marshall and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Red circle
Preprint: archiving forbidden
Green circle
Postprint: archiving allowed
Upload
Red circle
Published version: archiving forbidden
Policy details
Data provided by SHERPA/RoMEO

Abstract

Cluster of differentiation 1c (CD1c)-dependent self-reactive T cells are abundant in human blood, but self-antigens presented by CD1c to the T-cell receptors of these cells are poorly understood. Here we present a crystal structure of CD1c determined at 2.4 Å revealing an extended ligand binding potential of the antigen groove and a substantially different conformation compared with known CD1c structures. Computational simulations exploring different occupancy states of the groove reenacted these different CD1c conformations and suggested cholesteryl esters (CE) and acylated steryl glycosides (ASG) as new ligand classes for CD1c. Confirming this, we show that binding of CE and ASG to CD1c enables the binding of human CD1c self-reactive T-cell receptors. Hence, human CD1c adopts different conformations dependent on ligand occupancy of its groove, with CE and ASG stabilizing CD1c conformations that provide a footprint for binding of CD1c self-reactive T-cell receptors.