Receptor transfer between immune cells by autoantibody-enhanced, CD32-driven trogocytosis is hijacked by HIV-1 to infect resting CD4 T cells

Manuel Albanese ^1,2,20, Hong-Ru Chen ^1,20,∗, Madeleine Gapp ^1,20, Maximilian Muenchhoff ^1,3, Hsiu-Hui Yang ¹, David Peterhoff ⁴, Katja Hoffmann ⁵, Qianhao Xiao ¹, Adrian Ruhle ¹, Ina Ambiel ^6,7, Stephanie Schneider ¹, Ernesto Mejías-Pérez ¹, Marcel Stern ¹, Paul R Wratil ¹, Katharina Hofmann ¹, Laura Amann ¹, Linda Jocham ¹, Thimo Fuchs ¹, Alessandro F Ulivi ⁸, Simon Besson-Girard ⁹, Simon Weidlich ¹⁰, Jochen Schneider ¹⁰, Christoph D Spinner ^3,10, Kathrin Sutter ¹¹, Ulf Dittmer ¹¹, Andreas Humpe ¹², Philipp Baumeister ¹³, Andreas Wieser ^3,14,15, Simon Rothenfusser ¹⁶, Johannes Bogner ^3,17, Julia Roider ^3,17, Percy Knolle ^3,18, Hartmut Hengel ⁵, Ralf Wagner ⁴, Vibor Laketa ^7,19, Oliver T Fackler ^6,7,∗∗, Oliver T Keppler ^{1,3,21,∗∗∗}

Summary

Immune cell phenotyping frequently detects lineage-unrelated receptors. Here, we report that surface receptors can be transferred from primary macrophages to CD4 T cells and identify the Fcγ receptor CD32 as driver and cargo of this trogocytotic transfer. Filamentous CD32⁺ nanoprotrusions deposit distinct plasma membrane patches onto target T cells. Transferred receptors confer cell migration and adhesion properties, and macrophage-derived membrane patches render resting CD4 T cells susceptible to infection by serving as hotspots for HIV-1 binding. Antibodies that recognize T cell epitopes enhance CD32-mediated trogocytosis. Such autoreactive anti-HIV-1 envelope antibodies can be found in the blood of HIV-1 patients and, consistently, the percentage of CD32⁺ CD4 T cells is increased in their blood. This CD32-mediated, antigen-independent cell communication mode transiently expands the receptor repertoire and functionality of immune cells. HIV-1 hijacks this mechanism by triggering the generation of trogocytosis-promoting autoantibodies to gain access to immune cells critical to its persistence.

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Keywords: immune cell communication, trogocytosis, CD32, autoantibodies, HIV reservoir, CRISPR-Cas9

Publication History:
Cell Rep Med. 2024 Apr 4;5(4):101483. doi: 10.1016/j.xcrm.2024.101483

Footnotes:
Supplemental information can be found online at https://doi.org/10.1016/j.xcrm.2024.101483.