Ligand-induced interactions between butyrophilin 2A1 and 3A1 internal domains in the HMBPP receptor complex

Hsiao, Chia‐Hung Christine; Nguyen, Khiem; Jin, Yiming; Vinogradova, Olga; Wiemer, Andrew J.

doi:10.1016/j.chembiol.2022.01.004

Cited by 27 publications

(30 citation statements)

References 34 publications

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“…PAg does not bind to the Vγ9Vδ2TCR but needs “presentation” by other cells that is initiated by binding to the intracellular B30.2 domain of BTN3A1 ( 9 ). The PAg-binding induces a conformational change which leads to the formation of a BTN3A1-BTN2A1 complex and to a not yet understood change at the cell surface, which is recognized by the Vγ9Vδ2 T cells ( 27 ). Whether recognition involves direct binding of BTN3A1 to the TCR or a hypothetical counter receptor on the T cells, or both, is unclear, but the key role of both proteins in PAg-stimulation is undisputed.…”

Section: Phosphoantigen-reactive Vγ9vδ2 T Cells and Butyrophilinsmentioning

confidence: 99%

Butyrophilins: γδ T Cell Receptor Ligands, Immunomodulators and More

Herrmann

Karunakaran

2022

Front. Immunol.

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Butyrophilins (BTN) are relatives of the B7 family (e.g., CD80, PD-L1). They fulfill a wide range of functions including immunomodulation and bind to various receptors such as the γδ T cell receptor (γδTCR) and small molecules. One intensively studied molecule is BTN3A1, which binds via its cytoplasmic B30.2 domain, metabolites of isoprenoid synthesis, designated as phosphoantigen (PAg), The enrichment of PAgs in tumors or infected cells is sensed by Vγ9Vδ2 T cells, leading to the proliferation and execution of effector functions to remove these cells. This article discusses the contribution of BTNs, the related BTNL molecules and SKINT1 to the development, activation, and homeostasis of γδ T cells and their immunomodulatory potential, which makes them interesting targets for therapeutic intervention.

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Section: Phosphoantigen-reactive Vγ9vδ2 T Cells and Butyrophilinsmentioning

confidence: 99%

Butyrophilins: γδ T Cell Receptor Ligands, Immunomodulators and More

Herrmann

Karunakaran

2022

Front. Immunol.

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“…The protocol described below lists the steps for using human Vγ9Vδ2 T cells to detect antigens loaded into K562 leukemia cells ( Kilcollins et al., 2016 ; Hsiao and Wiemer, 2018 ; Hsiao et al., 2022 ). The Vγ9Vδ2 T cells are first expanded from buffy coat peripheral blood mononuclear cells (PBMCs).…”

Section: Before You Beginmentioning

confidence: 99%

“…Because the Vγ9Vδ2 T cell receptor recognizes the HMBPP receptor, the most important attribute of the phosphoantigen-containing cells is expression of the receptor, which is a complex of butyrophilin (BTN) 3A1 and 2A1 ( Karunakaran et al., 2020 ; Rigau et al., 2020 ; Vyborova et al., 2020 ; Cano et al., 2021 ; Hsiao et al., 2022 ). Because the phosphoantigen binding site on BTN3A1 is intracellular rather than extracellular ( Hsiao et al., 2014 ; Sandstrom et al., 2014 ; Rhodes et al., 2015 ; Wang and Morita, 2015 ; Peigne et al., 2017 ), we refer to the cells as antigen containing cells.…”

Section: Before You Beginmentioning

confidence: 99%

“…While specifically focused on cytokine production, this protocol can be readily adapted to evaluate other effector functions of activated Vγ9Vδ2 T cells. For complete details on the use and execution of this protocol, please refer to Hsiao et al. (2022) and Hsiao and Wiemer (2018) .…”

mentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Hsiao et al. (2022) and Hsiao and Wiemer (2018) .…”

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confidence: 99%

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Generation of effector Vγ9Vδ2 T cells and evaluation of their response to phosphoantigen-loaded cells

Hsiao

Wiemer

2022

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Effective γδ T‐cell clinical therapies: current limitations and future perspectives for cancer immunotherapy

Revesz,

Joyce,

Ebert

et al. 2024

Clin & Trans Imm

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Abstractγδ T cells are a unique subset of T lymphocytes, exhibiting features of both innate and adaptive immune cells and are involved with cancer immunosurveillance. They present an attractive alternative to conventional T cell‐based immunotherapy due, in large part, to their lack of major histocompatibility (MHC) restriction and ability to secrete high levels of cytokines with well‐known anti‐tumour functions. To date, clinical trials using γδ T cell‐based immunotherapy for a range of haematological and solid cancers have yielded limited success compared with in vitro studies. This inability to translate the efficacy of γδ T‐cell therapies from preclinical to clinical trials is attributed to a combination of several factors, e.g. γδ T‐cell agonists that are commonly used to stimulate populations of these cells have limited cellular uptake yet rely on intracellular mechanisms; administered γδ T cells display low levels of tumour‐infiltration; and there is a gap in the understanding of γδ T‐cell inhibitory receptors. This review explores the discrepancy between γδ T‐cell clinical and preclinical performance and offers viable avenues to overcome these obstacles. Using more direct γδ T‐cell agonists, encapsulating these agonists into lipid nanocarriers to improve their pharmacokinetic and pharmacodynamic profiles and the use of combination therapies to overcome checkpoint inhibition and T‐cell exhaustion are ways to bridge the gap between preclinical and clinical success. Given the ability to overcome these limitations, the development of a more targeted γδ T‐cell agonist‐checkpoint blockade combination therapy has the potential for success in clinical trials which has to date remained elusive.

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Ligand-induced interactions between butyrophilin 2A1 and 3A1 internal domains in the HMBPP receptor complex

Cited by 27 publications

References 34 publications

Butyrophilins: γδ T Cell Receptor Ligands, Immunomodulators and More

Butyrophilins: γδ T Cell Receptor Ligands, Immunomodulators and More

Generation of effector Vγ9Vδ2 T cells and evaluation of their response to phosphoantigen-loaded cells

Effective γδ T‐cell clinical therapies: current limitations and future perspectives for cancer immunotherapy

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