3MA7

Crystal structure of Cardiolipin bound to mouse CD1D

Summary for 3MA7

• Entry DOI: 10.2210/pdb3ma7/pdb
• Related: 1Z5L 2AKR 2Q7Y
• Descriptor: T-cell surface glycoprotein CD1d1, Beta-2 microglobulin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: gamma delta t cells, glycolipid presentation, mhc, cd1, cell membrane, endosome, glycoprotein, immune response, immunoglobulin domain, innate immunity, lysosome, membrane, transmembrane, mhc i, secreted, immune system, disulfide bond, immunity
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 4
• Total formula weight: 93076.56

Authors

Zajonc, D.M. (deposition date: 2010-03-23, release date: 2011-03-16, Last modification date: 2024-11-06)

Primary citation

Dieude, M.,Striegl, H.,Tyznik, A.J.,Wang, J.,Behar, S.M.,Piccirillo, C.A.,Levine, J.S.,Zajonc, D.M.,Rauch, J.
Cardiolipin Binds to CD1d and Stimulates CD1d-Restricted {gamma}{delta} T Cells in the Normal Murine Repertoire.
J.Immunol., 186:4771-4781, 2011

PubMed Abstract: Cardiolipin (CL), a major phospholipid in bacterial cell walls, is sequestered from the immune system in mammalian mitochondria and is, therefore, a potential danger signal. Based on growing evidence that phospholipids constitute natural ligands for CD1 and that CD1d-restricted T cells recognize phospholipids, we hypothesized that CD1d binds and presents CL and that T cells in the normal immune repertoire respond to CL in a CD1d-restricted manner. We determined the murine CD1d-CL crystal structure at 2.3 Å resolution and established through additional lipid loading experiments that CL, a tetra-acylated phospholipid, binds to murine CD1d with two alkyl chains buried inside the CD1d binding groove and the remaining two exposed into the solvent. We furthermore demonstrate the functional stimulatory activity of CL, showing that splenic and hepatic γδ T cells from healthy mice proliferate in vitro in response to mammalian or bacterial CL in a dose-dependent and CD1d-restricted manner, rapidly secreting the cytokines IFN-γ and RANTES. Finally, we show that hepatic γδ T cells are activated in vivo by CD1d-bearing dendritic cells that have been pulsed with CL, but not phosphatidylcholine. Together, these findings demonstrate that CD1d is able to bind and present CL to a subset of CL-responsive γδ T cells that exist in the spleen and liver of healthy mice and suggest that these cells could play a role in host responses to bacterial lipids and, potentially, self-CL. We propose that CL-responsive γδ T cells play a role in immune surveillance during infection and tissue injury.

PubMed: 21389252
DOI: 10.4049/jimmunol.1000921

Experimental method

X-RAY DIFFRACTION (2.29 Å)