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

• Published in: The Journal of immunology (1950) 2003-07, Vol.171 (1), p.32-36
• Main Authors: Schjetne, Karoline W, Thompson, Keith M, Nilsen, Nadra, Flo, Trude H, Fleckenstein, Burkhard, Iversen, Jens-Gustav, Espevik, Terje, Bogen, Bjarne
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antibodies, Monoclonal - metabolism; Antibodies, Monoclonal - pharmacology; Antibody Specificity; Antigen Presentation - genetics; Antigen-Presenting Cells - cytology; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigens - genetics; Antigens - metabolism; Bacterial Vaccines - immunology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Line; Clone Cells; Endocytosis - genetics; Endocytosis - immunology; Endosomes - immunology; Endosomes - metabolism; Epitopes, T-Lymphocyte - metabolism; Humans; Immunity, Active; Immunity, Innate; Immunoglobulin Constant Regions - metabolism; Immunoglobulin kappa-Chains - metabolism; Ligands; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Molecular Sequence Data; Receptors, Cell Surface - genetics; Receptors, Cell Surface - immunology; Receptors, Cell Surface - metabolism; Toll-Like Receptor 2; Toll-Like Receptors
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.1.32

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.