3ma7
Crystal structure of Cardiolipin bound to mouse CD1D
Structural highlights
FunctionCD1D1_MOUSE Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.[1] [2] [3] Publication Abstract from PubMedCardiolipin (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 A 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 gammadelta 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-gamma and RANTES. Finally, we show that hepatic gammadelta 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 gammadelta 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 gammadelta T cells play a role in immune surveillance during infection and tissue injury. Cardiolipin Binds to CD1d and Stimulates CD1d-Restricted {gamma}{delta} T Cells in the Normal Murine Repertoire.,Dieude M, Striegl H, Tyznik AJ, Wang J, Behar SM, Piccirillo CA, Levine JS, Zajonc DM, Rauch J J Immunol. 2011 Apr 15;186(8):4771-81. Epub 2011 Mar 9. PMID:21389252[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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