Taking It Slow

Science Signaling  14 Oct 2008:
Vol. 1, Issue 41, pp. ec356
DOI: 10.1126/scisignal.141ec356

Engagement of T cell receptors (TCRs) on CD8+ T cells by antigenic peptide-bound class I major histocompatability complexes (MHCs) on dendritic cells leads to T cell activation, which is important for the immune response to viral infections. Serial engagement of multiple TCRs on a T cell by the same peptide-MHC complex (pMHC) is thought to trigger the accumulation of sufficient downstream signals to lead to T cell activation. Maturation of DCs in response to microbial products such as lipopolysaccharide (LPS) or unmethylated CpG oligonucleotides, which stimulate Toll-like receptors (TLRs), is required for optimal activation of T cells. Rudd et al. investigated how pretreatment of antigen-pulsed mouse bone marrow-derived DCs with CpG oligonucleotides affected activation of TCR transgenic CD8+ T cells in vitro. More CD8+ T cells were activated when cocultured with CpG-treated antigen-pulsed DCs than were activated when exposed to untreated antigen-pulsed DCs. Although treatment of DCs with CpGs increased the abundance of MHC complexes on the DCs, the authors showed that, when normalized for the abundance of pMHC complexes, CpG-treated DCs still resulted in increased activation of CD8+ T cells compared with that by untreated DCs. Other TLR ligands resulted in the same outcome. Treatment of DCs with CpG oligonucleotides increased the half-life of their pMHC complexes compared with those of untreated DCs, which then enabled the triggering of increased numbers of TCRs on the CD8+ T cells. These data suggest that stabilization of pMHC complexes is another mechanism by which TLR ligands modulate T cell activation, which is relevant to their roles as adjuvants for vaccines.

B. D. Rudd, J. D. Brien, M. P. Davenport, J. Nikolich-Žugich, Cutting edge: TLR ligands increase TCR triggering by slowing peptide-MHC class I decay rates. J. Immunol. 181, 5199-5203 (2008). [PubMed]