ULBP1, 2, 3: novel MHC class I-related molecules that bind to human cytomegalovirus glycoprotein UL16, activate NK cells.
New members of the extended MHC class I-like family were identified based on their ability to bind human cytomegalovirus glycoprotein UL16 and/or their mutual homology. Soluble UL16 binding proteins (ULBP) competed with each other for binding to NK cells. Treatment of human and mouse NK cells with ULBP led to increased production of cytokines/chemokines, proliferation, cytotoxic activity and up-regulation of activation-associated surface molecules. The presence of ULBP during the stimulation phase of the CTL assay caused increased cytotoxic activity. Addition of soluble recombinant UL16 protein inhibited the biological activities mediated by ULBP, suggesting the existence of a novel mechanism utilized by CMV to evade elimination by the host immune system.
Kubin
M
M
Department of Immunobiology, Immunex Corporation, Seattle 98101, USA. mkubin@immunex.com
Cassiano
L
L
Chalupny
J
J
Chin
W
W
Cosman
D
D
Fanslow
W
W
Müllberg
J
J
Rousseau
A M
AM
Ulrich
D
D
Armitage
R
R
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins; D019409:Interleukin-15 / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D008565:Membrane Proteins; D051379:Mice; D016513:Mice, SCID; D011485:Protein Binding; D012995:Solubility; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014759:Viral Envelope Proteins / Q000378:metabolism* / Q000494:pharmacology
D002352:Carrier Proteins; D018925:Chemokines; D016207:Cytokines; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins; D019409:Interleukin-15; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C423231:ULBP1 protein, human; C423230:ULBP2 protein, human; C423229:ULBP3 protein, human; D014759:Viral Envelope Proteins