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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: MacDonald, Alana, Lam, Brandon, Lin, John, Ferrall, Louise, Kung, Yu Jui, Tsai, Ya Chea, Wu, T.-C., Hung, Chien-Fu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599986/
https://www.ncbi.nlm.nih.gov/pubmed/34804041
http://dx.doi.org/10.3389/fimmu.2021.755995
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author MacDonald, Alana
Lam, Brandon
Lin, John
Ferrall, Louise
Kung, Yu Jui
Tsai, Ya Chea
Wu, T.-C.
Hung, Chien-Fu
author_facet MacDonald, Alana
Lam, Brandon
Lin, John
Ferrall, Louise
Kung, Yu Jui
Tsai, Ya Chea
Wu, T.-C.
Hung, Chien-Fu
author_sort MacDonald, Alana
collection PubMed
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.
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spelling pubmed-85999862021-11-19 Delivery of IL-2 to the T Cell Surface Through Phosphatidylserine Permits Robust Expansion of CD8 T Cells MacDonald, Alana Lam, Brandon Lin, John Ferrall, Louise Kung, Yu Jui Tsai, Ya Chea Wu, T.-C. Hung, Chien-Fu Front Immunol Immunology 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. Frontiers Media S.A. 2021-11-04 /pmc/articles/PMC8599986/ /pubmed/34804041 http://dx.doi.org/10.3389/fimmu.2021.755995 Text en Copyright © 2021 MacDonald, Lam, Lin, Ferrall, Kung, Tsai, Wu and Hung https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
MacDonald, Alana
Lam, Brandon
Lin, John
Ferrall, Louise
Kung, Yu Jui
Tsai, Ya Chea
Wu, T.-C.
Hung, Chien-Fu
Delivery of IL-2 to the T Cell Surface Through Phosphatidylserine Permits Robust Expansion of CD8 T Cells
title 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_short 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
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599986/
https://www.ncbi.nlm.nih.gov/pubmed/34804041
http://dx.doi.org/10.3389/fimmu.2021.755995
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