Ever wished as a kid that you were just that little bit older so that you could get into the club that everyone was talking about? The alternative to maturity for many a teenager has long been presentation — dress yourself up and hope no one asks your age. Successful entry to an adaptive immune response also depends on these two factors. The maturation of antigen-presenting cells, such as dendritic cells (DCs), aids the stimulation of CD4+ T cells, as does enhanced presentation of antigen on the MHC class II molecules of DCs. This study shows that Toll-like receptor 2 (TLR2) has an important role in both of these processes.

Signalling through TLR2 induces the maturation of DCs, but can ligands bound to TLR2 be internalized for presentation by MHC class II molecules? Schjetne and colleagues used an antagonistic TLR2-specific monoclonal antibody with κ light chains (TL2.1), which acts as a ligand for TLR2 without inducing signalling, to separate the maturation-inducing effects of TLR2 stimulation from the antigen-presenting effects. First, they showed that TL2.1 failed to induce the maturation of immature DCs. However, TL2.1 was still 100–1,000 times more efficient at stimulating the proliferation of Cκ-specific CD4+ T cells by antibody-treated DCs than was an isotype-matched control antibody. In the absence of DC maturation, enhanced presentation of the Cκ epitope of TL2.1 by DCs must be responsible for the T-cell stimulation. The effect was shown to be specific for TLR2 binding, as antibodies specific for CD62 ligand or CXC chemokine receptor 1 did not enhance T-cell proliferation.

The response of Cκ-specific T cells to TL2.1 was almost completely abrogated by the addition of chloroquine, leupeptin or brefeldin A, which inhibit different stages in the lysosomal processing and presentation of MHC class II antigens. This indicates that ligands bound to TLR2 enter the conventional pathway for presentation by MHC class II molecules. This conclusion is supported by the authors' demonstration by fluorescent staining of the entry of TL2.1 into early endosomes.

It seems probable, therefore, that stimulation of TLR2 in vivo would lead to the development of an adaptive immune response by synergy between DC maturation and the enhanced presentation of antigens to T cells. This makes TLR2 an attractive target for vaccines. To get the right response, it seems to help if you are mature enough and dress like it.