Expression of the NKG2D ligand UL16 binding protein-1 (ULBP-1) on dendritic cells.
Innate and adaptive immunity have not evolved separately. In this regard, the NKG2D molecule first identified on NK cells and classified as an activating NK cell receptor is also an important receptor for CD8(+) T cells. Functional analyses of human NKG2D and its ligands, i.e. UL16 binding proteins (ULBP) and MHC class I chain-related (MIC), have so far focused on immune cell-target cell situations because of the expression of NKG2D ligands on infected, stressed or transformed cells. Here, however, we address a possible function of NKG2D/ULBP-1 during the initiation of T cell responses. ULBP-1 can be detected on mature dendritic cells both in situ in the T cell areas of lymph nodes as well as in vitro after artificial maturation. FCM analysis further demonstrated that although NKG2D is expressed to some degree on all analyzed T cell subsets from peripheral blood, in vitro stimulation of T cells results in up-regulation of NKG2D on proliferating T cells. Using the sentinel lymph nodes of primary melanoma as a model for induction of defined T cell responses in vivo, we were able to demonstrate the expression of NKG2D on melanoma-associated antigen-specific T cells. Thus, our results suggest a role for NGK2D-ULBP-1 in the induction or reactivation of T cell responses.
Schrama
David
D
Department of Dermatology, Julius Maximilians-University, Würzburg, Germany.
Terheyden
Patrick
P
Otto
Kerstin
K
Kämmerer
Ulrike
U
Bröcker
Eva-Bettina
EB
Lühder
Fred
F
Cosman
David
D
Andersen
Mads Hald
MH
Becker
Jürgen C
JC
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008545:Melanoma / Q000276:immunology; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D021701:Sentinel Lymph Node Biopsy; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D002352:Carrier Proteins; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C423231:ULBP1 protein, human