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Lymphocytes, B and T cells, are immune cells that protect us against diseases. Lymphocytes use special immunoreceptors in the cell surface to recognize pathogens, to communicate with other cells, and to migrate through the body. Researchers (Laia Querol-Cano, Vera-Marie Dunlock, Fabian Schwerdtfeger and Annemiek van Spriel) from the Dept. of Medical BioSciences review how immunoreceptors are organized at the cell surface of lymphocytes by specialized membrane organizer proteins, tetraspanins and galectins. Understanding cell surface organization of immune cells may provide exciting new therapeutic opportunities.
Immunoreceptors are not randomly distributed at the plasma membrane of lymphocytes but are segregated into specialized domains that function as platforms to initiate signaling, as exemplified by the B cell or T cell receptor complex and the immunological synapse. Tetraspanins and galectins are crucial for controlling the spatiotemporal organization of immunoreceptors and other signaling proteins. Deficiencies in specific tetraspanins and galectins result in impaired immune synapse formation, lymphocyte proliferation, antibody production and migration, which can lead to impaired immunity, tumor development and autoimmunity. In contrast to conventional ligand–receptor interactions, membrane organizers interact in cis (on the same cell) and modulate receptor clustering, receptor dynamics and intracellular signaling. New findings have uncovered their complex and dynamic nature, revealing shared binding partners and collaborative activity in determining the composition of membrane domains. Therefore, immunoreceptors should not be envisaged as independent entities and instead should be studied in the context of their spatial organization in the lymphocyte membrane.
Read the full publication here
Membrane organization by tetraspanins and galectins shapes lymphocyte function.
Querol Cano L, Dunlock VE, Schwerdtfeger F, van Spriel AB. Nat Rev Immunol. 2023 Sep 27.
doi: 10.1038/s41577-023-00935-0.
