Presentation: A Tick’s Grip on Immunity: Structural Determinants of Salp15–CD4 Interaction and effect on human CD4+ T cells

Ticks are obligate hematophagous ectoparasites that rely on salivary proteins to evade host immune defences during blood feeding. Tick saliva contains a complex mixture of bioactive molecules, including potent immunomodulators. Among the best-studied is Salp15, a 15-kDa salivary protein from Ixodes scapularis with strong immunosuppressive properties. In murine models, Salp15 has been shown to bind CD4 on T cells, thereby interfering with T-cell receptor-mediated signalling and inhibiting CD4⁺ T-cell activation, proliferation, and cytokine production. While these functional effects are well documented in mice, the molecular basis underlying Salp15 activity and its relevance to human T-cell responses remain poorly understood. To address this, we aim to elucidate the structural determinants underlying Salp15 activity by resolving its three-dimensional structure and characterizing its interaction with CD4 and potential additional cellular targets using nuclear magnetic resonance (NMR) spectroscopy. In parallel, we investigate the immunomodulatory effects of recombinant Salp15 on human CD4⁺ T cells. Defining the structural and functional determinants of Salp15 activity will provide critical insight into its mechanism of immune modulation and may support the rational development of Salp15-derived molecules as novel immunomodulatory agents for immune-mediated diseases.