Kinetics and cellular site of glycolipid loading control the outcome of natural killer T cell activation.
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 alpha galactosylceramide (alphaGalCer) 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 alphaGalCer-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 alphaGalCer 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.
Im
Jin S
JS
Department of Microbiology and Immunology , Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Arora
Pooja
P
Bricard
Gabriel
G
Molano
Alberto
A
Venkataswamy
Manjunatha M
MM
Baine
Ian
I
Jerud
Elliot S
ES
Goldberg
Michael F
MF
Baena
Andres
A
Yu
Karl O A
KO
Ndonye
Rachel M
RM
Howell
Amy R
AR
Yuan
Weiming
W
Cresswell
Peter
P
Chang
Young-Tae
YT
Illarionov
Petr A
PA
Besra
Gurdyal S
GS
Porcelli
Steven A
SA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D055610:Antigens, CD1d / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D005699:Galactosylceramides / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
D055610:Antigens, CD1d; D016207:Cytokines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide