title: Binding strength and dynamics of invariant natural killer cell T cell receptor/CD1d-glycosphingolipid interaction on living cells by single molecule force spectroscopy.
abstract: Invariant natural killer T (iNKT) cells are a population of T lymphocytes that play an important role in regulating immunity to infection and tumors by recognizing endogenous and exogenous CD1d-bound lipid molecules. Using soluble iNKT T cell receptor (TCR) molecules, we applied single molecule force spectroscopy for the investigation of the iNKT TCR affinity for human CD1d molecules loaded with glycolipids differing in the length of the phytosphingosine chain using either recombinant CD1d molecules or lipid-pulsed THP1 cells. In both settings, the dissociation of the iNKT TCR from human CD1d molecules loaded with the lipid containing the longer phytosphingosine chain required higher unbinding forces compared with the shorter phytosphingosine lipid. Our findings are discussed in the context of previous results obtained by surface plasmon resonance measurements. We present new insights into the energy landscape and the kinetic rate constants of the iNKT TCR/human CD1d-glycosphingolipid interaction and emphasize the unique potential of single molecule force spectroscopy on living cells.
authors: Institute for Biophysics, Johannes Kepler University, Linz, Austria.
authors: Bianca L
authors: BL
authors: Bozna
authors: Paolo
authors: P
authors: Polzella
authors: Christian
authors: C
authors: Rankl
authors: Rong
authors: R
authors: Zhu
authors: Mariolina
authors: M
authors: Salio
authors: Dawn
authors: D
authors: Shepherd
authors: Memed
authors: M
authors: Duman
authors: Vincenzo
authors: V
authors: Cerundolo
authors: Peter
authors: P
authors: Hinterdorfer
mesh_terms: D055610:Antigens, CD1d / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D006028:Glycosphingolipids / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry* / Q000276:immunology; D007700:Kinetics; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D013057:Spectrum Analysis
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human; D006028:Glycosphingolipids; D011948:Receptors, Antigen, T-Cell