title: MHC class II molecules enhance Toll-like receptor mediated innate immune responses.
abstract: BACKGROUND
  Major 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.
  
  
  RESULTS
  We 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-beta-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
  These 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.
authors.affiliation: Division of Immunology/Allergology, University of Zurich, Children's Hospital, Zurich, Switzerland. remo.frei@kispi.uzh.ch
authors.forename: Remo
authors.initials: R
authors.lastname: Frei
authors.forename: Johanna
authors.initials: J
authors.lastname: Steinle
authors.forename: Thomas
authors.initials: T
authors.lastname: Birchler
authors.forename: Susanne
authors.initials: S
authors.lastname: Loeliger
authors.forename: Caroline
authors.initials: C
authors.lastname: Roduit
authors.forename: Dirk
authors.initials: D
authors.lastname: Steinhoff
authors.forename: Reinhart
authors.initials: R
authors.lastname: Seibl
authors.forename: Katja
authors.initials: K
authors.lastname: Büchner
authors.forename: Reinhard
authors.initials: R
authors.lastname: Seger
authors.forename: Walter
authors.initials: W
authors.lastname: Reith
authors.forename: Roger P
authors.initials: RP
authors.lastname: Lauener
mesh_terms: D000818:Animals; D002460:Cell Line; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*
chemical_list: D000949:Histocompatibility Antigens Class II; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4