MHC class II molecules enhance Toll-like receptor mediated innate immune responses.
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.
Frei
Remo
R
Division of Immunology/Allergology, University of Zurich, Children's Hospital, Zurich, Switzerland. remo.frei@kispi.uzh.ch
Steinle
Johanna
J
Birchler
Thomas
T
Loeliger
Susanne
S
Roduit
Caroline
C
Steinhoff
Dirk
D
Seibl
Reinhart
R
Büchner
Katja
K
Seger
Reinhard
R
Reith
Walter
W
Lauener
Roger P
RP
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*
D000949:Histocompatibility Antigens Class II; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4