Heparin-sensitive receptor on dendritic cells

The heparin-sensitive receptor on dendritic cells is a critical mediator of the high immunogenicity and associated toxicity of Adenovirus serotype 5 (Ad5) viral vectors. Unlike the primary CAR receptor used for epithelial infection, this receptor interacts specifically with the KKTK motif in the Ad5 fiber shaft, allowing the virus to efficiently transduce dendritic cells and initiate potent T-cell and B-cell responses. This pathway is the molecular basis for the effectiveness of many Ad5-based vaccines, including those for COVID-19 and Ebola, but it also triggers the release of pyrogenic cytokines that cause transient fevers in clinical trial participants. While often referred to by its sensitivity to heparin inhibition, the receptor's identity is closely linked to proteins such as DC-SIGN (CD209) and L-selectin (CD62L), which facilitate viral attachment and entry in the absence of traditional receptors. Understanding this interaction is vital for engineering safer, next-generation viral vectors that maintain immunogenicity while minimizing systemic inflammatory side effects.

Other names

Heparin-sensitive Ad5 receptorAd5 fiber shaft receptorKKTK-binding receptorL-selectin (CD62L)DC-SIGN (CD209)

Binding of the Adenovirus fiber shaft KKTK motif to the receptor facilitates viral entry into dendritic cells, leading to antigen presentation and stimulation of adaptive immunity, while simultaneously triggering pro-inflammatory signaling and pyrogenic responses.