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CD1c antigen presentation

Mansour, Salah and Tocheva, Anna and Cave-Ayland, Chris and Machelett, Moritz and Sander, Barbara and Lissin, Nikolai and Molloy, Peter and Baird, Mark and Stübs, Gunthard and Schröder, Nicolas and Schumann, Ralf and Rademann, Jörg and Postle, Anthony and Jakobsen, Bent and Marshall, Ben and Gosain, Rajendra and Elkington, Paul and Elliott, Tim and Skylaris, Chris and Essex, Jonathan and Tews, Ivo and Gadola, Stephan (2016) CD1c antigen presentation. Cholesteryl esters stabilise human CD1c conformations for recognition by self-reactive T cells.

Abstract

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 unknown. 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 to known CD1c structures. Computational simulations exploring different occupancy states of the groove re-enacted 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 stabilising CD1c conformations that provide a footprint for binding of CD1c self-reactive T cell receptors.

Item Type: Article
Date Deposited: 26 Apr 2016 23:45
Last Modified: 26 Apr 2016 23:45
URI: https://oak.novartis.com/id/eprint/27635

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