Imaging of biphasic signalosomes constructed by checkpoint receptor 2B4 in conventional and chimeric antigen receptor-T cells.

ABSTRACT: A co-signaling receptor, 2B4, has dual effects in immune cells, but its actual functions in T cells remain elusive. Here, using super-resolution imaging technology with an immunological synapse model, we showed that 2B4 forms "2B4 microclusters" immediately after 2B4-CD48 binding. A lipid phosphatase, SHIP-1, subsequently combined with 2B4 to form coinhibitory signalosomes, leading to the suppression of cytokine production. An activating adapter, SLAM-associated protein (SAP), attenuated the clustering of SHIP-1 and recruited a kinase, Fyn, enhancing the Vav1 signaling pathway as costimulatory signalosomes. Furthermore, we found that a chimeric antigen receptor with a 2B4 tail (2B4-CAR) retained the original signal transduction mechanism of 2B4. With endogenous levels of SAP expression, 2B

SUBMITTER: Matsushima R 

PROVIDER: S-EPMC11780131 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature