Delivery 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 h...

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Autores principales:	Alana MacDonald, Brandon Lam, John Lin, Louise Ferrall, Yu Jui Kung, Ya Chea Tsai, T.-C. Wu, Chien-Fu Hung
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	phosphatidylserine (PS) annexin V interleukin 2 (IL 2) CD8 T cells activation Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/6267ec4e7c5b4195b90c716ff716f756
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spelling	oai:doaj.org-article:6267ec4e7c5b4195b90c716ff716f7562021-11-04T06:49:25ZDelivery of IL-2 to the T Cell Surface Through Phosphatidylserine Permits Robust Expansion of CD8 T Cells1664-322410.3389/fimmu.2021.755995https://doaj.org/article/6267ec4e7c5b4195b90c716ff716f7562021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.755995/fullhttps://doaj.org/toc/1664-3224The 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). In vitro analysis revealed that AnnV-IL2 is able to specifically bind PS on the T cell surface following TCR stimulation. Consequently, AnnV-IL2 proved to be significantly more effective at enhancing T cell activation compared to recombinant IL-2. In vivo, AnnV-IL2 promotes robust expansion of antigen-specific cells capable of interferon gamma (IFNγ) production when administered following peptide vaccination. Importantly, upon antigen rechallenge, AnnV-IL2 treatment mice demonstrated a stronger secondary expansion, indicating durability of AnnV-IL2 mediated responses. Our data supports the use of AnnV-IL2 to modulate antigen-specific T cell immunity and demonstrates that the PS-AnnV axis is a feasible mechanism to target diverse cargo to CD8 T cells.Alana MacDonaldAlana MacDonaldBrandon LamBrandon LamJohn LinLouise FerrallYu Jui KungYa Chea TsaiT.-C. WuT.-C. WuChien-Fu HungChien-Fu HungFrontiers Media S.A.articlephosphatidylserine (PS)annexin Vinterleukin 2 (IL 2)CD8 T cellsactivationImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	phosphatidylserine (PS) annexin V interleukin 2 (IL 2) CD8 T cells activation Immunologic diseases. Allergy RC581-607
spellingShingle	phosphatidylserine (PS) annexin V interleukin 2 (IL 2) CD8 T cells activation Immunologic diseases. Allergy RC581-607 Alana MacDonald Alana MacDonald Brandon Lam Brandon Lam John Lin Louise Ferrall Yu Jui Kung Ya Chea Tsai T.-C. Wu T.-C. Wu Chien-Fu Hung Chien-Fu Hung Delivery of IL-2 to the T Cell Surface Through Phosphatidylserine Permits Robust Expansion of CD8 T Cells
description	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). In vitro analysis revealed that AnnV-IL2 is able to specifically bind PS on the T cell surface following TCR stimulation. Consequently, AnnV-IL2 proved to be significantly more effective at enhancing T cell activation compared to recombinant IL-2. In vivo, AnnV-IL2 promotes robust expansion of antigen-specific cells capable of interferon gamma (IFNγ) production when administered following peptide vaccination. Importantly, upon antigen rechallenge, AnnV-IL2 treatment mice demonstrated a stronger secondary expansion, indicating durability of AnnV-IL2 mediated responses. Our data supports the use of AnnV-IL2 to modulate antigen-specific T cell immunity and demonstrates that the PS-AnnV axis is a feasible mechanism to target diverse cargo to CD8 T cells.
format	article
author	Alana MacDonald Alana MacDonald Brandon Lam Brandon Lam John Lin Louise Ferrall Yu Jui Kung Ya Chea Tsai T.-C. Wu T.-C. Wu Chien-Fu Hung Chien-Fu Hung
author_facet	Alana MacDonald Alana MacDonald Brandon Lam Brandon Lam John Lin Louise Ferrall Yu Jui Kung Ya Chea Tsai T.-C. Wu T.-C. Wu Chien-Fu Hung Chien-Fu Hung
author_sort	Alana MacDonald
title	Delivery of IL-2 to the T Cell Surface Through Phosphatidylserine Permits Robust Expansion of CD8 T Cells
title_short	Delivery of IL-2 to the T Cell Surface Through Phosphatidylserine Permits Robust Expansion of CD8 T Cells
title_full	Delivery of IL-2 to the T Cell Surface Through Phosphatidylserine Permits Robust Expansion of CD8 T Cells
title_fullStr	Delivery of IL-2 to the T Cell Surface Through Phosphatidylserine Permits Robust Expansion of CD8 T Cells
title_full_unstemmed	Delivery of IL-2 to the T Cell Surface Through Phosphatidylserine Permits Robust Expansion of CD8 T Cells
title_sort	delivery of il-2 to the t cell surface through phosphatidylserine permits robust expansion of cd8 t cells
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6267ec4e7c5b4195b90c716ff716f756
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Delivery of IL-2 to the T Cell Surface Through Phosphatidylserine Permits Robust Expansion of CD8 T Cells

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