Assessing the function of human UNC-93B in Toll-like receptor signaling and major histocompatibility complex II response.
The high sequence identity observed between UNC-93B of mouse and human imply common evolutionary ancestors and a conserved function. A nonconservative point mutation in the mouse Unc93b1 gene has been associated with defective Toll-like receptor (TLR) signaling and impaired major histocompatibility complex (MHC) I and II restricted antigen responses. Like murine UNC-93B, the human homologue is predicted to form 12 transmembrane domains, and it localizes to the endoplasmic reticulum. In human beings its expression is highest in professional antigen-presenting cells such as dendritic cells and macrophages. Interestingly, UNC-93B itself is specifically induced by TLR3 signaling in monocyte-derived dendritic cells and macrophages. To study the effect of UNC-93B deficiency in TLR signaling and antigen-presentation in human beings, UNC-93B message was knocked down in monocyte-derived dendritic cells and a reduced TNFalpha production in response to TLR3 agonists was observed. In the same experiment, the achieved knockdown had no effect on an MHC II-dependent antigen response, suggesting that the reduced quantity of human UNC-93B was still capable of supporting class II antigen presentation or that UNC-93B is not required for class II antigen presentation in human antigen-presenting cells.
Koehn
Jadranka
J
Novartis Institutes for BioMedical Research, Vienna, Austria.
Huesken
Dieter
D
Jaritz
Markus
M
Rot
Antal
A
Zurini
Mauro
M
Dwertmann
Anne
A
Beutler
Bruce
B
Korthäuer
Ulf
U
D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D026901:Membrane Transport Proteins; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C454130:UNC93B1 protein, human; D018799:Intercellular Adhesion Molecule-1