Cutting edge: link between innate and adaptive immunity: Toll-like receptor 2 internalizes antigen for presentation to CD4+ T cells and could be an efficient vaccine target.
An ideal vaccine for induction of CD4(+) T cell responses should induce local inflammation, maturation of APC, and peptide loading of MHC class II molecules. Ligation of Toll-like receptor (TLR) 2 provides the first two of these three criteria. We have studied whether targeting of TLR2 results in loading of MHC class II molecules and enhancement of CD4(+) T cell responses. To dissociate MHC class II presentation from APC maturation, we have used an antagonistic, mouse anti-human TLR2 mAb (TL2.1) as ligand and measured proliferation of a mouse Ckappa-specific human CD4(+) T cell clone. TL2.1 mAb was 100-1000 times more efficiently presented by APC compared with isotype-matched control mAb. Moreover, TL2.1 mAb was internalized into endosomes and processed by the conventional MHC class II pathway. This novel function of TLR2 represents a link between innate and adaptive immunity and indicates that TLR2 could be a promising target for vaccines.
Schjetne
Karoline W
KW
Institute of Immunology, University of Oslo, Rikshospitalet, Oslo, Norway. k.w.schjetne@labmed.uio.no
Thompson
Keith M
KM
Nilsen
Nadra
N
Flo
Trude H
TH
Fleckenstein
Burkhard
B
Iversen
Jens-Gustav
JG
Espevik
Terje
T
Bogen
Bjarne
B
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D000918:Antibody Specificity; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000235:genetics / Q000378:metabolism*; D001428:Bacterial Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells; D004705:Endocytosis / Q000235:genetics / Q000276:immunology*; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D006801:Humans; D007110:Immunity, Active; D007113:Immunity, Innate; D007127:Immunoglobulin Constant Regions / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D000911:Antibodies, Monoclonal; D000941:Antigens; D001428:Bacterial Vaccines; D018984:Epitopes, T-Lymphocyte; D007127:Immunoglobulin Constant Regions; D007145:Immunoglobulin kappa-Chains; D008024:Ligands; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors