Kinetics and Cellular Site of Glycolipid Loading Control the Outcome of Natural Killer T Cell Activation

JS Im; P Arora; G Bricard; A Molano; MM Venkataswamy; I Baine; ES Jerud; MF Goldberg; A Baena; KOA Yu; RM Ndonye; AR Howell; W Yuan; P Cresswell; YT Chang; Petr Illarionov; Gurdyal Besra; SA Porcelli

doi:10.1016/j.immuni.2009.03.022

Kinetics and Cellular Site of Glycolipid Loading Control the Outcome of Natural Killer T Cell Activation

JS Im, P Arora, G Bricard, A Molano, MM Venkataswamy, I Baine, ES Jerud, MF Goldberg, A Baena, KOA Yu, RM Ndonye, AR Howell, W Yuan, P Cresswell, YT Chang, Petr Illarionov, Gurdyal Besra, SA Porcelli

Biosciences

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Abstract

CD1d-restricted natural killer T cells (NKT cells) possess a wide range of effector and regulatory activities that are related to their ability to secrete both T helper 1 (Th1) cell- and Th2 cell-type cytokines. We analyzed presentation of NKT cell activating α galactosylceramide (αGalCer) analogs that give predominantly Th2 cell-type cytokine responses to determine how ligand structure controls the outcome of NKT cell activation. Using a monoclonal antibody specific for αGalCer-CD1d complexes to visualize and quantitate glycolipid presentation, we found that Th2 cell-type cytokinebiasing ligands were characterized by rapid and direct loading of cell-surface CD1d proteins. Complexes formed by association of these Th2 cell-type cytokine-biasing αGalCer analogs with CD1d showed a distinctive exclusion from ganglioside-enriched, detergent-resistant plasma membrane microdomains of antigen-presenting cells. These findings help to explain how subtle alterations in glycolipid ligand structure can control the balance of proinflammatory and antiinflammatory activities of NKT cells.

Original language	English
Pages (from-to)	888-898
Number of pages	11
Journal	Immunity
Volume	30
Issue number	6
DOIs	https://doi.org/10.1016/j.immuni.2009.03.022
Publication status	Published - 1 Jun 2009

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Modulation of Immune Responses by aGalCer Analogues Through Differential Activation of CD1d-restricted NKT Cells
Besra, D. & Lammas, T.
Medical Research Council
1/06/05 → 30/11/09
Project: Research Councils

Cite this

Im, JS., Arora, P., Bricard, G., Molano, A., Venkataswamy, MM., Baine, I., Jerud, ES., Goldberg, MF., Baena, A., Yu, KOA., Ndonye, RM., Howell, AR., Yuan, W., Cresswell, P., Chang, YT., Illarionov, P., Besra, G., & Porcelli, SA. (2009). Kinetics and Cellular Site of Glycolipid Loading Control the Outcome of Natural Killer T Cell Activation. Immunity, 30(6), 888-898. https://doi.org/10.1016/j.immuni.2009.03.022

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title = "Kinetics and Cellular Site of Glycolipid Loading Control the Outcome of Natural Killer T Cell Activation",

abstract = "CD1d-restricted natural killer T cells (NKT cells) possess a wide range of effector and regulatory activities that are related to their ability to secrete both T helper 1 (Th1) cell- and Th2 cell-type cytokines. We analyzed presentation of NKT cell activating α galactosylceramide (αGalCer) analogs that give predominantly Th2 cell-type cytokine responses to determine how ligand structure controls the outcome of NKT cell activation. Using a monoclonal antibody specific for αGalCer-CD1d complexes to visualize and quantitate glycolipid presentation, we found that Th2 cell-type cytokinebiasing ligands were characterized by rapid and direct loading of cell-surface CD1d proteins. Complexes formed by association of these Th2 cell-type cytokine-biasing αGalCer analogs with CD1d showed a distinctive exclusion from ganglioside-enriched, detergent-resistant plasma membrane microdomains of antigen-presenting cells. These findings help to explain how subtle alterations in glycolipid ligand structure can control the balance of proinflammatory and antiinflammatory activities of NKT cells.",

author = "JS Im and P Arora and G Bricard and A Molano and MM Venkataswamy and I Baine and ES Jerud and MF Goldberg and A Baena and KOA Yu and RM Ndonye and AR Howell and W Yuan and P Cresswell and YT Chang and Petr Illarionov and Gurdyal Besra and SA Porcelli",

year = "2009",

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doi = "10.1016/j.immuni.2009.03.022",

language = "English",

volume = "30",

pages = "888--898",

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Im, JS, Arora, P, Bricard, G, Molano, A, Venkataswamy, MM, Baine, I, Jerud, ES, Goldberg, MF, Baena, A, Yu, KOA, Ndonye, RM, Howell, AR, Yuan, W, Cresswell, P, Chang, YT, Illarionov, P, Besra, G & Porcelli, SA 2009, 'Kinetics and Cellular Site of Glycolipid Loading Control the Outcome of Natural Killer T Cell Activation', Immunity, vol. 30, no. 6, pp. 888-898. https://doi.org/10.1016/j.immuni.2009.03.022

TY - JOUR

T1 - Kinetics and Cellular Site of Glycolipid Loading Control the Outcome of Natural Killer T Cell Activation

AU - Im, JS

AU - Arora, P

AU - Bricard, G

AU - Molano, A

AU - Venkataswamy, MM

AU - Baine, I

AU - Jerud, ES

AU - Goldberg, MF

AU - Baena, A

AU - Yu, KOA

AU - Ndonye, RM

AU - Howell, AR

AU - Yuan, W

AU - Cresswell, P

AU - Chang, YT

AU - Illarionov, Petr

AU - Besra, Gurdyal

AU - Porcelli, SA

PY - 2009/6/1

Y1 - 2009/6/1

N2 - CD1d-restricted natural killer T cells (NKT cells) possess a wide range of effector and regulatory activities that are related to their ability to secrete both T helper 1 (Th1) cell- and Th2 cell-type cytokines. We analyzed presentation of NKT cell activating α galactosylceramide (αGalCer) analogs that give predominantly Th2 cell-type cytokine responses to determine how ligand structure controls the outcome of NKT cell activation. Using a monoclonal antibody specific for αGalCer-CD1d complexes to visualize and quantitate glycolipid presentation, we found that Th2 cell-type cytokinebiasing ligands were characterized by rapid and direct loading of cell-surface CD1d proteins. Complexes formed by association of these Th2 cell-type cytokine-biasing αGalCer analogs with CD1d showed a distinctive exclusion from ganglioside-enriched, detergent-resistant plasma membrane microdomains of antigen-presenting cells. These findings help to explain how subtle alterations in glycolipid ligand structure can control the balance of proinflammatory and antiinflammatory activities of NKT cells.

AB - CD1d-restricted natural killer T cells (NKT cells) possess a wide range of effector and regulatory activities that are related to their ability to secrete both T helper 1 (Th1) cell- and Th2 cell-type cytokines. We analyzed presentation of NKT cell activating α galactosylceramide (αGalCer) analogs that give predominantly Th2 cell-type cytokine responses to determine how ligand structure controls the outcome of NKT cell activation. Using a monoclonal antibody specific for αGalCer-CD1d complexes to visualize and quantitate glycolipid presentation, we found that Th2 cell-type cytokinebiasing ligands were characterized by rapid and direct loading of cell-surface CD1d proteins. Complexes formed by association of these Th2 cell-type cytokine-biasing αGalCer analogs with CD1d showed a distinctive exclusion from ganglioside-enriched, detergent-resistant plasma membrane microdomains of antigen-presenting cells. These findings help to explain how subtle alterations in glycolipid ligand structure can control the balance of proinflammatory and antiinflammatory activities of NKT cells.

U2 - 10.1016/j.immuni.2009.03.022

DO - 10.1016/j.immuni.2009.03.022

M3 - Article

C2 - 19538930

SN - 1097-4180

VL - 30

SP - 888

EP - 898

JO - Immunity

JF - Immunity

IS - 6

ER -

Kinetics and Cellular Site of Glycolipid Loading Control the Outcome of Natural Killer T Cell Activation

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Modulation of Immune Responses by aGalCer Analogues Through Differential Activation of CD1d-restricted NKT Cells

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