MHC Class II Molecules Enhance Toll-Like Receptor Mediated Innate Immune Responses |
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Authors: | Remo Frei Johanna Steinle Thomas Birchler Susanne Loeliger Caroline Roduit Dirk Steinhoff Reinhart Seibl Katja Büchner Reinhard Seger Walter Reith Roger P Lauener |
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Institution: | 1. Division of Immunology/Allergology, University of Zurich, Children''s Hospital, Zurich, Switzerland.; 2. Section of Clinical Immunology, University Hospital Zurich, Zurich, Switzerland.; 3. Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.;Massachusetts General Hospital/Harvard University, United States of America |
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Abstract: | BackgroundMajor histocompatibility complex (MHC) class II molecules play crucial roles in immune activation by presenting foreign peptides to antigen-specific T helper cells and thereby inducing adaptive immune responses. Although adaptive immunity is a highly effective defense system, it takes several days to become fully operational and needs to be triggered by danger-signals generated during the preceding innate immune response. Here we show that MHC class II molecules synergize with Toll-like receptor (TLR) 2 and TLR4 in inducing an innate immune response.Methodology/Principal FindingsWe found that co-expression of MHC class II molecules and TLR2 or TLR4 in human embryonic kidney (HEK) cells 293 leads to enhanced production of the anti-microbial peptide human-β-defensin (hBD) 2 after treatment with TLR2 stimulus bacterial lipoprotein (BLP) or TLR4 ligand lipopolysaccharide (LPS), respectively. Furthermore, we found that peritoneal macrophages of MHC class II knock-out mice show a decreased responsiveness to TLR2 and TLR4 stimuli compared to macrophages of wild-type mice. Finally, we show that MHC class II molecules are physically and functionally associated with TLR2 in lipid raft domains of the cell membrane.Conclusions/SignificanceThese results demonstrate that MHC class II molecules are, in addition to their central role in adaptive immunity, also implicated in generating optimal innate immune responses. |
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