Recognition of lyso-phospholipids by human natural killer T lymphocytes.
Natural killer T (NKT) cells are a subset of T lymphocytes with potent immunoregulatory properties. Recognition of self-antigens presented by CD1d molecules is an important route of NKT cell activation; however, the molecular identity of specific autoantigens that stimulate human NKT cells remains unclear. Here, we have analyzed human NKT cell recognition of CD1d cellular ligands. The most clearly antigenic species was lyso-phosphatidylcholine (LPC). Diacylated phosphatidylcholine and lyso-phosphoglycerols differing in the chemistry of the head group stimulated only weak responses from human NKT cells. However, lyso-sphingomyelin, which shares the phosphocholine head group of LPC, also activated NKT cells. Antigen-presenting cells pulsed with LPC were capable of stimulating increased cytokine responses by NKT cell clones and by freshly isolated peripheral blood lymphocytes. These results demonstrate that human NKT cells recognize cholinated lyso-phospholipids as antigens presented by CD1d. Since these lyso-phospholipids serve as lipid messengers in normal physiological processes and are present at elevated levels during inflammatory responses, these findings point to a novel link between NKT cells and cellular signaling pathways that are associated with human disease pathophysiology.
Fox
Lisa M
LM
Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Cox
Daryl G
DG
Lockridge
Jennifer L
JL
Wang
Xiaohua
X
Chen
Xiuxu
X
Scharf
Louise
L
Trott
David L
DL
Ndonye
Rachel M
RM
Veerapen
Natacha
N
Besra
Gurdyal S
GS
Howell
Amy R
AR
Cook
Mark E
ME
Adams
Erin J
EJ
Hildebrand
William H
WH
Gumperz
Jenny E
JE
D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D055610:Antigens, CD1d / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008213:Lymphocyte Activation; D008244:Lysophosphatidylcholines / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000276:immunology; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives / Q000276:immunology
D055610:Antigens, CD1d; D001324:Autoantigens; C526877:CD1D protein, human; D016207:Cytokines; D008244:Lysophosphatidylcholines; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D013110:Sphingosine