Effects of lipid chain lengths in alpha-galactosylceramides on cytokine release by natural killer T cells.
Glycolipid presentation by CD1 proteins has emerged as an important aspect of antigen recognition, and presentation of alpha-glycosylceramides by CD1d to natural killer T cells has become a central focus in understanding how glycolipid presentation can influence immune responses. An alpha-galactosylceramide containing relatively long lipid chains has been the subject of intense study because, when presented by CD1d to natural killer T cells, it stimulates the release of both proinflammatory and immunomodulatory cytokines. Using an efficient synthesis of alpha-galactosylceramides, we have prepared a series of glycolipids in which the lipid chain lengths have been incrementally varied. The responses of natural killer T cells to these glycolipids have been determined, and we have found that truncation of the phytosphingosine lipid chain increases the relative amounts of immunomodulatory cytokines released. In similar fashion, the length of the acyl chain in alpha-galactosylceramides influences cytokine release profiles.
Goff
Randal D
RD
Brigham Young University, Provo, Utah 84602, USA.
Gao
Ying
Y
Mattner
Jochen
J
Zhou
Dapeng
D
Yin
Ning
N
Cantu
Carlos
C
Teyton
Luc
L
Bendelac
Albert
A
Savage
Paul B
PB
D000818:Animals; D017951:Antigen Presentation; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005699:Galactosylceramides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; D005699:Galactosylceramides