Author:
Mansour Salah,Tocheva Anna S.,Cave-Ayland Chris,Machelett Moritz M.,Sander Barbara,Lissin Nikolai M.,Molloy Peter E.,Baird Mark S.,Stübs Gunthard,Schröder Nicolas W. J.,Schumann Ralf R.,Rademann Jörg,Postle Anthony D.,Jakobsen Bent K.,Marshall Ben G.,Gosain Rajendra,Elkington Paul T.,Elliott Tim,Skylaris Chris-Kriton,Essex Jonathan W.,Tews Ivo,Gadola Stephan D.
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.
Funder
Higher Education Funding Council for England
Publisher
Proceedings of the National Academy of Sciences
Cited by
42 articles.
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