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

Jin S. Im; Pooja Arora; Gabriel Bricard; Alberto Molano; Manjunatha M. Venkataswamy; Ian Baine; Elliot S. Jerud; Michael F. Goldberg; Andres Baena; Karl O.A. Yu; Rachel M. Ndonye; Amy R. Howell; Weiming Yuan; Peter Cresswell; Young tae Chang; Petr A. Illarionov; Gurdyal S. Besra; Steven A. 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

Jin S. Im
, Pooja Arora
, Gabriel Bricard
, Alberto Molano
, Manjunatha M. Venkataswamy
, Ian Baine
, Elliot S. Jerud
, Michael F. Goldberg
, Andres Baena
, Karl O.A. Yu
, Rachel M. Ndonye
, Amy R. Howell
, Weiming Yuan
, Peter Cresswell
, Young tae Chang
, Petr A. Illarionov
, Gurdyal S. Besra
, Steven A. Porcelli

Pediatrics

Albert Einstein College of Medicine
University of Connecticut
Yale University
National University of Singapore
University of Birmingham

Research output: Contribution to journal › Article › peer-review

162 Scopus citations

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 cytokine-biasing 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 anti-inflammatory 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
State	Published - Jun 19 2009

Keywords

CELLIMMUNO
MOLIMMUNO

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10.1016/j.immuni.2009.03.022

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Im, J. S., Arora, P., Bricard, G., Molano, A., Venkataswamy, M. M., Baine, I., Jerud, E. S., Goldberg, M. F., Baena, A., Yu, K. O. A., Ndonye, R. M., Howell, A. R., Yuan, W., Cresswell, P., Chang, Y. T., Illarionov, P. A., Besra, G. S., & Porcelli, S. A. (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

@article{d2a6b592c4c44eed8139a1b5eb57d89c,

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 cytokine-biasing 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 anti-inflammatory activities of NKT cells.",

keywords = "CELLIMMUNO, MOLIMMUNO",

author = "Im, \{Jin S.\} and Pooja Arora and Gabriel Bricard and Alberto Molano and Venkataswamy, \{Manjunatha M.\} and Ian Baine and Jerud, \{Elliot S.\} and Goldberg, \{Michael F.\} and Andres Baena and Yu, \{Karl O.A.\} and Ndonye, \{Rachel M.\} and Howell, \{Amy R.\} and Weiming Yuan and Peter Cresswell and Chang, \{Young tae\} and Illarionov, \{Petr A.\} and Besra, \{Gurdyal S.\} and Porcelli, \{Steven A.\}",

year = "2009",

month = jun,

day = "19",

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

language = "English",

volume = "30",

pages = "888--898",

journal = "Immunity",

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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, PA, Besra, GS & 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, Jin S.

AU - Arora, Pooja

AU - Bricard, Gabriel

AU - Molano, Alberto

AU - Venkataswamy, Manjunatha M.

AU - Baine, Ian

AU - Jerud, Elliot S.

AU - Goldberg, Michael F.

AU - Baena, Andres

AU - Yu, Karl O.A.

AU - Ndonye, Rachel M.

AU - Howell, Amy R.

AU - Yuan, Weiming

AU - Cresswell, Peter

AU - Chang, Young tae

AU - Illarionov, Petr A.

AU - Besra, Gurdyal S.

AU - Porcelli, Steven A.

PY - 2009/6/19

Y1 - 2009/6/19

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 cytokine-biasing 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 anti-inflammatory 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 cytokine-biasing 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 anti-inflammatory activities of NKT cells.

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KW - MOLIMMUNO

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DO - 10.1016/j.immuni.2009.03.022

M3 - Article

C2 - 19538930

AN - SCOPUS:66949155720

SN - 1074-7613

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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Keywords

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