Nonglycosidic CD1d lipid ligands activate human and murine invariant NKT cells

被引：64

作者：

Silk, Jonathan D. ^{[1
]}

Salio, Mariolina ^{[1
]}

Reddy, B. Gopal ^{[2
]}

Shepherd, Dawn ^{[1
]}

Gileadi, Uzi ^{[1
]}

Brown, James ^{[3
]}

Masri, S. Hajar ^{[1
]}

Polzella, Paolo ^{[1
]}

Ritter, Gerd ^{[4
]}

Besra, Gurdyal S. ^{[5
]}

Jones, E. Yvonne ^{[3
]}

Schmidt, Richard R. ^{[2
]}

Cerundolo, Vincenzo ^{[1
]}

机构：

[1] John Radcliffe Hosp, Tumour Immunol Grp, Weatherall Inst Mol Med, Oxford OX3 9DU, England

[2] Univ Konstanz, Fachbereich Chem, Constance, Germany

[3] Univ Oxford, Canc Res UK Receptor Struct Res Grp, Div Struct Biol, Wellcome Trust Ctr Human Genet, Oxford, England

[4] Mem Sloan Kettering Canc Ctr, Ludwig Inst Canc Res, New York Branch, New York, NY 10065 USA

[5] Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England

来源：

JOURNAL OF IMMUNOLOGY | 2008年 / 180卷 / 10期

基金：

英国医学研究理事会;

关键词：

D O I：

10.4049/jimmunol.180.10.6452

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Invariant NKT cells (iNKT cells) recognize CD1d/glycolipid complexes. We demonstrate that the nonglycosidic compound threitolceramide efficiently activates iNKT cells, resulting in dendritic cell (DC) maturation and the priming of Ag-specific T and B cells. Threitolceramide-pulsed DCs are more resistant to iNKT cell-dependent lysis than alpha-galactosylceramide-pulsed DCs due to the weaker affinity of the human iNKT TCR for CD1d/threitolceramide than CD1d/alpha-galactosylceramide complexes. iNKT cells stimulated with threitolceramide also recover more quickly from activation-induced energy. Kinetic and functional experiments showed that shortening or lengthening the threitol moiety by one hydroxymethylene group modulates ligand recognition, as human and murine iNKT cells recognize glycerolceramide and arabinitolceramide differentially. Our data broaden the range of potential cell agonists. The ability of these compounds to assist the priming of Ag-specific immune responses while minimizing iNKT cell-dependent DC is makes them attractive adjuvants for vaccination strategies.

引用

页码：6452 / 6456

页数：5

共 24 条

[1] The biology of NKT cells [J].

Bendelac, Albert ;

Savage, Paul B. ;

Teyton, Luc .

ANNUAL REVIEW OF IMMUNOLOGY, 2007, 25 :297-336

[2] CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor [J].

Borg, Natalie A. ;

Wun, Kwok S. ;

Kjer-Nielsen, Lars ;

Wilce, Matthew C. J. ;

Pellicci, Daniel G. ;

Koh, Ruide ;

Besra, Gurdyal S. ;

Bharadwaj, Mandvi ;

Godfrey, Dale I. ;

McCluskey, James ;

Rossjohn, Jamie .

NATURE, 2007, 448 (7149) :44-49

[3] CD1d ligands: The good, the bad and the ugly [J].

Brutkiewicz, Randy R. .

JOURNAL OF IMMUNOLOGY, 2006, 177 (02) :769-775

[4] Activation of natural killer T cells by α-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein [J].

Fujii, S ;

Shimizu, K ;

Smith, C ;

Bonifaz, L ;

Steinman, RM .

JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (02) :267-279

[5] Structure and binding kinetics of three different human CD1d-α-agalactosylceramide-specific T cell receptors [J].

Gadola, SD ;

Koch, M ;

Marles-Wright, J ;

Lissin, NM ;

Shepherd, D ;

Matulis, G ;

Harlos, K ;

Villiger, PM ;

Stuart, DI ;

Jakobsen, BK ;

Cerundolo, V ;

Jones, EY .

JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (03) :699-710

[6] Vα24-JαQ-independent, CD1d-restricted recognition of α-galactosylceramide by human CD4+ and CD8αβ+ T lymphocytes [J].

Gadola, SD ;

Dulphy, N ;

Salio, M ;

Cerundolo, V .

JOURNAL OF IMMUNOLOGY, 2002, 168 (11) :5514-5520

[7] Invariant NKT cells sustain specific B cell responses and memory [J].

Galli, Grazia ;

Pittoni, Paola ;

Tonti, Elena ;

Malzone, Carmine ;

Uematsu, Yasushi ;

Tortoli, Marco ;

Maione, Domenico ;

Volpini, Gianfranco ;

Finco, Oretta ;

Nuti, Sandra ;

Tavarini, Simona ;

Dellabona, Paolo ;

Rappuoli, Rino ;

Casorati, Giulia ;

Abrignani, Sergio .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (10) :3984-3989

[8] Dendritic cell function can be modulated through cooperative actions of TLR ligands and invariant NKT cells [J].

Hermans, Ian F. ;

Silk, Jonathan D. ;

Gileadi, Uzi ;

Masri, S. Hajar ;

Shepherd, Dawn ;

Farrand, Kathryn J. ;

Salio, Mariolina ;

Cerundolo, Vincenzo .

JOURNAL OF IMMUNOLOGY, 2007, 178 (05) :2721-2729

[9] The VITAL assay: a versatile fluorometric technique for assessing CTL- and NKT-mediated cytotoxicity against multiple targets in vitro and in vivo [J].

Hermans, IF ;

Silk, JD ;

Yang, JP ;

Palmowski, MJ ;

Gileadi, U ;

McCarthy, C ;

Salio, M ;

Ronchese, F ;

Cerundolo, V .

JOURNAL OF IMMUNOLOGICAL METHODS, 2004, 285 (01) :25-40

[10] NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells [J].

Hermans, IF ;

Silk, JD ;

Gileadi, U ;

Salio, M ;

Mathew, B ;

Ritter, G ;

Schmidt, R ;

Harris, AL ;

Old, L ;

Cerundolo, V .

JOURNAL OF IMMUNOLOGY, 2003, 171 (10) :5140-5147

← 1 2 3 →