Comeau, S. | bioRxiv Science

bioRxiv2023

Benthic diversity along an Arctic fjord: which are the key factors?

Arctic coastal ecosystems include benthic communities that hold an important role within the marine food chain. Kelps, fucoid species, and coralline algae dominate rocky habitats, offering food and shelter for various species. Kelps and fucoid species also aid in carbon sequestration, sediment stabilization, and erosion mitigation. In summer, the influx of freshwater from glacier and permafrost melt alters coastal waters conditions. The input of turbid freshwater influences underwater light, salinity, and substrate, impacting benthic organism distribution. This study investigates possible link between environmental conditions and benthic diversity through environmental DNA (eDNA). Six sites were monitored along Kongsfjorden (Svalbard,Norway) during the summer of 2021. Contrary to expectations, macroalgal distribution didnt correlate with light, and suspension feeders showed no clear links with chlorophyll a or nutrient concentrations. Glacial influence may have contributed to higher benthic diversity. Predators presence, tied to glacier proximity, possibly explained this trend. However, further studies are needed to validate these observations and assumptions.

ecology↗

bioRxiv2022

Segmental flexibility of bispecific T-cell engagers regulates the dynamics of immune synapse formation

Bispecific T-cell engagers (TcEs) link T cell receptors to tumor-associated antigens on cancer cells, forming cytotoxic immunological synapses (IS). Close membrane-to-membrane contact ([≤]13 nm) has been proposed as a key mechanism of TcE function. To investigate this and identify potential additional mechanisms, we compared four immunoglobulin G1-based (IgG1) TcE Formats (A-D) targeting CD3{varepsilon} and Her2, designed to create varying intermembrane distances (A B=C>D. In a minimal system for IS formation on SLBs, TcE performance followed the trend A=B=C>D. Addition of close-contact requiring CD58 co-stimulation revealed phospholipase C-{gamma} activation matching cytotoxicity with A>B=C>D. Our findings suggest that, when adhesion is equivalent, TcE potency is determined by two parameters: contact distance and flexibility. Both the close/far-contact formation axis and the low/high flexibility axis significantly impact TcE potency, explaining the similar potency of Format B (close-contact/high flexibility) and C (far-contact/low flexibility). Significance statementBispecific T-cell engagers (TcEs) are immunotherapeutic drugs that trigger the destruction of cancer cells by linking T cells to cancer cell through specific surface molecules (antigens). We designed a series of TcEs with varying distances between their binding sites and flexibilities of the TcE-antigen complexes. By combining structural and functional analyses, we confirmed close-contact formation between T cells and cancer cells as a critical determinant, mediated by co-activating receptors. Furthermore, we also identified molecular flexibility of the TcE-antigen complex as a further critical parameter for TcE potency. These findings provide novel insights into TcE function and highlight the importance of both parameters for future research and the design of improved immunotherapies.

immunology↗