Toll-like receptor 2 ligands as adjuvants for human Th1 responses.
Bacterial lipopeptides (bLPs) are increasingly used as adjuvants to activate cell-mediated immune responses to foreign Ags. To explore mechanisms whereby bLPs adjuvant T cell responses, we stimulated human PBMCs with bLPs. We found that bLPs stimulate T cells to proliferate and produce IFN-gamma in an accessory cell-dependent manner and in the absence of exogenous protein Ags. The ability of bLPs to stimulate T cell proliferation was Toll-like receptor 2 dependent and required IL-12, interaction with costimulatory molecules, and MHC proteins. Our data suggest that bLPs adjuvant adaptive Th1 responses by enhancing Ag presentation of endogenous peptides.
Sieling
Peter A
PA
Department of Medicine, Division of Dermatology, David Gefffen School of Medicine, University of California, Los Angeles, CA 90095, USA. psieling@mednet.ucla.edu
Chung
Woosin
W
Duong
Baochau T
BT
Godowski
Paul J
PJ
Modlin
Robert L
RL
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000502:physiology*; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D051940:B7-2 Antigen; D001426:Bacterial Proteins / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D029721:Drosophila Proteins; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008074:Lipoproteins / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014210:Treponema pallidum / Q000276:immunology
C090573:47-kDa immunogen, Treponema pallidum; D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D051940:B7-2 Antigen; D001426:Bacterial Proteins; C497964:CD86 protein, human; D002352:Carrier Proteins; D016207:Cytokines; D029721:Drosophila Proteins; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D018664:Interleukin-12