Modulation of human natural killer T cell ligands on TLR-mediated antigen-presenting cell activation.
Invariant natural killer T (iNKT) cells are a subset of nonconventional T cells recognizing endogenous and/or exogenous glycolipid antigens in the context of CD1d molecules. It remains unclear whether innate stimuli can modify the profile of endogenous lipids recognized by iNKT cells on the surface of antigen-presenting cells (APCs). We report that activation of human APCs by Toll-like receptor ligands (TLR-L) modulates the lipid biosynthetic pathway, resulting in enhanced recognition of CD1d-associated lipids by iNKT cells, as defined by IFN-gamma secretion. APC-derived soluble factors further increase CD1d-restricted iNKT cell activation. Finally, using soluble tetrameric iNKT T cell receptors (TCR) as a staining reagent, we demonstrate specific up-regulation of CD1d-bound ligand(s) on TLR-mediated APC maturation. The ability of innate stimuli to modulate the lipid profile of APCs resulting in iNKT cell activation and APC maturation underscores the role of iNKT cells in assisting priming of antigen-specific immune responses.
Salio
Mariolina
M
Tumor Immunology Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom. mariolina.salio@imm.ox.ac.uk
Speak
Anneliese O
AO
Shepherd
Dawn
D
Polzella
Paolo
P
Illarionov
Petr A
PA
Veerapen
Natacha
N
Besra
Gurdyal S
GS
Platt
Frances M
FM
Cerundolo
Vincenzo
V
D000938:Antigen-Presenting Cells / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000819:agonists*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018949:Antigens, CD1; D006028:Glycosphingolipids; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma