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Updated: Oct 11, 2026

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
Published on: February 28, 2019
Poly-guanosine motifs costimulate antigen-reactive CD8 T cells while bacterial CpG-DNA affect T-cell activation via
G B Lipford1, S Bendigs, K Heeg
1Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.
Abstract:
Pathogen-derived pattern recognition ligands like lipopolysaccharide (LPS) and bacterial cytidine-guanosine (CpG)-DNA not only activate dendritic cells and macrophages but are also mitogenic for B cells. Less clear are the claimed effects of CpG-DNA on T cells, which range from direct activation, costimulation, or indirect transient activation via antigen-presenting cell (APC)-derived interferon type I (IFN type I). Here we demonstrate that CpG-DNA sequence specifically triggers macrophages to produce IFN type I, interleukin (IL)-12, IL-6 and tumour necrosis factor (TNF), but lacks the ability to directly costimulate T cells. Strikingly, poly-guanosine (poly-G) extensions to CpG-containing oligonucleotides (ODN) abolished the macrophage stimulatory potential yet generated T-cell costimulatory activities. In fact, independently of CpG-motifs, poly-G-ODN displayed the ability to costimulate T cells. Costimulation was operative on CD8 T cells but not CD4 T cells. Poly-G-mediated costimulation resulted in IL-2-driven T-cell proliferation and induced cytolytic T cells. Overall the data imply that poly-G motifs costimulate antigen reactive CD8 T cells, while CpG-DNA motifs fail to do so but may affect T-cell activation via APC derived cytokines such as IFN type I.
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