5C9J

Human CD1c with ligands in A' and F' channel

Summary for 5C9J

• Entry DOI: 10.2210/pdb5c9j/pdb
• Descriptor: T-cell surface glycoprotein CD1c,T-cell surface glycoprotein CD1b, Beta-2-microglobulin, LAURIC ACID, ... (7 entities in total)
• Functional Keywords: antigen presentation, cd1, human cd1, mhc-like, immunology, lipid antigen, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane ; Single- pass type I membrane protein : P29016; Secreted : P61769
• Total number of polymer chains: 2
• Total formula weight: 44463.82

Authors

Tews, I.,Machelett, M.M.,Mansour, S.,Gadola, S.D. (deposition date: 2015-06-27, release date: 2016-03-02, Last modification date: 2024-10-23)

Primary citation

Mansour, S.,Tocheva, A.S.,Cave-Ayland, C.,Machelett, M.M.,Sander, B.,Lissin, N.M.,Molloy, P.E.,Baird, M.S.,Stubs, G.,Schroder, N.W.,Schumann, R.R.,Rademann, J.,Postle, A.D.,Jakobsen, B.K.,Marshall, B.G.,Gosain, R.,Elkington, P.T.,Elliott, T.,Skylaris, C.K.,Essex, J.W.,Tews, I.,Gadola, S.D.
Cholesteryl esters stabilize human CD1c conformations for recognition by self-reactive T cells.
Proc.Natl.Acad.Sci.USA, 113:E1266-E1275, 2016

PubMed 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.

PubMed: 26884207
DOI: 10.1073/pnas.1519246113

Experimental method

X-RAY DIFFRACTION (2.4 Å)