Related Experiment Video

Updated: Aug 18, 2026

Using a GFP-tagged TMEM184A Construct for Confirmation of Heparin Receptor Identity
10:41

Using a GFP-tagged TMEM184A Construct for Confirmation of Heparin Receptor Identity

Published on: February 17, 2017

Toll-like receptor-dependent activation of several human blood cell types by protamine-condensed mRNA

Birgit Scheel1, Regina Teufel, Jochen Probst

  • 1CureVac GmbH, Tübingen, Germany.

European Journal of Immunology
|April 16, 2005
PubMed

Insights

Protamine-stabilized RNA acts as a potent danger signal, activating immune cells and potentially serving as a vaccine. This discovery advances mRNA-based immunotherapies by combining antigen production with immunostimulation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Vaccine Development

Background:

  • RNA condensed on protamine is protected from degradation and has vaccine potential.
  • The immune-activating properties of these complexes are not fully understood.

Purpose of the Study:

  • To investigate the immune-activating properties of protamine-stabilized RNA.
  • To elucidate the cellular pathways involved in this activation.
  • To explore the potential of these complexes in immunotherapy.

Main Methods:

  • Activation of mouse and human immune cells with protamine-RNA complexes.
  • Analysis of cytokine secretion (TNF-alpha, IFN-alpha).
  • Investigation of MyD88-dependent pathways and potential TLR involvement.

Main Results:

  • Protamine-RNA complexes act as danger signals activating mouse cells via MyD88.
  • Human blood cells, including dendritic cells (DC) and monocytes, are strongly activated.
  • B cells, NK cells, and granulocytes are also directly activated, with potential TLR-7/8 involvement.

Conclusions:

  • Protamine-stabilized RNA is a strong danger signal, similar to viral RNA.
  • These complexes combine antigen production with non-specific immunostimulation.
  • This explains their vaccine capacity and supports mRNA-based immunotherapy development.

More Related Videos

A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry04:32

A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry

Published on: June 5, 2019

Screening Peptides that Activate MRGPRX2 using Engineered HEK Cells12:38

Screening Peptides that Activate MRGPRX2 using Engineered HEK Cells

Published on: November 6, 2021

Related Concept Videos

Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...