"Cell-to-Cell “Sharing” as a Viral Shortcut: Trogocytosis in HIV infection" - Dr Manuel Albanese
Manuel Albanese earned his MSc in Medical Biotechnology and Molecular Medicine (University of Milan, 2013) and his PhD in Biology at LMU Munich (2014–2017) in Prof. Hammerschmidt’s lab (Helmholtz Center Munich), studying Epstein–Barr virus microRNAs and immune evasion. He then joined Prof. Keppler’s group at the Max von Pettenkofer-Institut (LMU, 2017–2021) to investigate HIV infection and persistence, receiving the LMU Excellence–Junior Researcher Fund, FöFoLe, Friedrich-Baur-Stiftung, and the DAIG Young Researcher Award. In 2021 he returned to Italy for a postdoc in Prof. Lanzavecchia’s lab (INGM), optimizing T-cell immunotherapy via CRISPR/Cas9 modulation of activation and effector functions. Since 2023 he is Assistant Professor (RTD-B) at the University of Milan. Since June 2024 he is a Junior Group Leader at INGM, supported by AIRC MFAG and the Italian Fund for Science (FIS2), developing engineered extracellular vesicles to deliver effector proteins for cancer and antiviral therapies.
Immune cell phenotyping frequently detects lineage-unrelated receptors. Understanding how these receptors are regulated within immune cells is crucial for deciphering the nature and function of this unexpected receptor expression. We recently developed an optimized CRISPR/Cas9-based approach to knock out individual or multiple genes in primary cells, specifically B cells, macrophages and resting, non-proliferating T cells, achieving efficiencies of up to 100%. Using this approach, we discovered that certain proteins are transferred between T cells and other cell types in a bidirectional process called trogocytosis. We have characterized this process mechanistically and functionally, demonstrating that transferred receptors confer new migration and adhesion properties to recipient cells. Notably, individuals living with HIV exhibit increased circulating T cells with acquired receptors. In these patients, we identified autoantibodies capable of binding to T cells and drastically enhancing trogocytosis via Fc gamma receptors. Furthermore, these newly acquired membrane patches render resting CD4 T cells more susceptible to HIV-1 infection by serving as hotspots for viral binding. Thus, HIV-1 appears to hijack this mechanism by triggering the generation of trogocytosis-promoting autoantibodies to gain access to immune cells critical for its persistence. This novel, antigen-independent cell communication mode transiently expands the receptor repertoire and functionality of immune cells. Future research will explore the full scope of this process and its potential for therapeutic manipulation.
