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

J Immunol. 2003 Jul 1;171(1):32-6. doi: 10.4049/jimmunol.171.1.32.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Antibodies, Monoclonal
  • Antigens
  • Bacterial Vaccines
  • Epitopes, T-Lymphocyte
  • Immunoglobulin Constant Regions
  • Immunoglobulin kappa-Chains
  • Ligands
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • TLR2 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptors