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

被引：142

作者：

Im, Jin S. ^{[1
]}

Arora, Pooja ^{[1
]}

Bricard, Gabriel ^{[1
]}

Molano, Alberto ^{[1
]}

Venkataswamy, Manjunatha M. ^{[1
]}

Baine, Ian ^{[1
]}

Jerud, Elliot S. ^{[1
]}

Goldberg, Michael F. ^{[1
]}

Baena, Andres ^{[1
]}

Yu, Karl O. A. ^{[1
]}

Ndonye, Rachel M. ^{[3
]}

Howell, Amy R. ^{[3
]}

Yuan, Weiming ^{[4
,5
]}

Cresswell, Peter ^{[4
,5
]}

Chang, Young-tae ^{[6
,7
]}

Illarionov, Petr A. ^{[8
]}

Besra, Gurdyal S. ^{[8
]}

Porcelli, Steven A. ^{[1
,2
]}

机构：

[1] Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA

[2] Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA

[3] Univ Connecticut, Dept Chem, Storrs, CT 06269 USA

[4] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA

[5] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA

[6] Natl Univ Singapore, Dept Chem, Singapore 117543, Singapore

[7] Natl Univ Singapore, Inst Life Sci, NUS MedChem Program, Singapore 117543, Singapore

[8] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England

来源：

IMMUNITY | 2009年 / 30卷 / 06期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

HUMAN CD1D MOLECULES; LIGAND ALPHA-GALACTOSYLCERAMIDE; II-PEPTIDE COMPLEXES; NKT CELLS; PLASMA-MEMBRANE; DENDRITIC CELLS; LIPID RAFTS; IN-VIVO; RECOGNITION; PROTEINS;

D O I：

10.1016/j.immuni.2009.03.022

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

CID1d-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 a galactosylceramide (alpha GalCer) 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 alpha GalCer-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 alpha GalCer 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.

引用

页码：888 / 898

页数：11

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