Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 14 October 2008
Vol. 1, Issue 41, p. ec356
[DOI: 10.1126/scisignal.141ec356]


Immunology Taking It Slow

John F. Foley

Science Signaling, AAAS, Washington, DC 20005, USA

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-Zugich, Cutting edge: TLR ligands increase TCR triggering by slowing peptide-MHC class I decay rates. J. Immunol. 181, 5199-5203 (2008). [PubMed]

Citation: J. F. Foley, Taking It Slow. Sci. Signal. 1, ec356 (2008).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882