biostudies-literatureMacDonald ANIDCR NIH HHSNCI NIH HHSNational Institutes of Health755995https://www.ebi.ac.uk/biostudies/studies/S-EPMC8599986biostudies-literatureUnknown12The phospholipid phosphatidylserine (PS) is naturally maintained on the cytoplasmic side of the plasma membrane. Independent of apoptosis, PS is redistributed to the surface of CD8 T cells in response to TCR-mediated activation. Annexin V (AnnV) is a protein known to bind PS with high affinity and has been effectively utilized to anchor antigen to the surface of CD8 T cells. To expand these studies, we aimed to exploit TCR activation driven PS exposure as a target to deliver cytokine, namely interleukin-2 (IL-2), to the surface of CD8 T cells. This was accomplished using a novel chimeric fusion protein of annexin V and interleukin 2 (AnnV-IL2). <i>In vitro</i> analysis revealed that AnnV-IL2 is able to specifically bind PS on the T cell surface following TCR stimulation. Consequently, AnnVFrontiers in immunologyDelivery of IL-2 to the T Cell Surface Through Phosphatidylserine Permits Robust Expansion of CD8 T Cells.PMC8599986R21 DE029910NIH/NCI P50CA098252, NIH/NCI R01CA233486 , R21CA234516, R21DE029910, 5F31CA236051R01 CA233486P50 CA098252F31 CA236051R21 CA234516MacDonald ALam BHung CFKung YJLin JFerrall LTsai YCWu TCfalseDelivery of IL-2 to the T Cell Surface Through Phosphatidylserine Permits Robust Expansion of CD8 T Cells.The phospholipid phosphatidylserine (PS) is naturally maintained on the cytoplasmic side of the plasma membrane. Independent of apoptosis, PS is redistributed to the surface of CD8 T cells in response to TCR-mediated activation. Annexin V (AnnV) is a protein known to bind PS with high affinity and has been effectively utilized to anchor antigen to the surface of CD8 T cells. To expand these studies, we aimed to exploit TCR activation driven PS exposure as a target to deliver cytokine, namely interleukin-2 (IL-2), to the surface of CD8 T cells. This was accomplished using a novel chimeric fusion protein of annexin V and interleukin 2 (AnnV-IL2). <i>In vitro</i> analysis revealed that AnnV-IL2 is able to specifically bind PS on the T cell surface following TCR stimulation. Consequently, AnnV2021-01-01T00:00:00Z20212025-06-01T00:03:13.477Z2025-06-01T00:03:13.477ZS-EPMC85999863480404110.3389/fimmu.2021.755995