Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 871-878 |
| Number of pages | 8 |
| Journal | Human immunology |
| Volume | 68 |
| Issue number | 11 |
| Early online date | 24 Sept 2007 |
| DOIs | |
| Publication status | Published - Nov 2007 |
Keywords
- Antigen Presentation
- Antigen-Presenting Cells
- CD4-Positive T-Lymphocytes
- Cells, Cultured
- Cytokines
- Dendritic Cells
- Endoplasmic Reticulum
- Histocompatibility Antigens Class II
- Humans
- Intercellular Adhesion Molecule-1
- Lymphocyte Activation
- Macrophages
- Membrane Transport Proteins
- Signal Transduction
- Toll-Like Receptors
- Tumor Necrosis Factor-alpha