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A new α‐C‐galactosylceramide analog: promotion of Th1‐biased responses in human CD1d‐reactive Vα24‐invariant natural killer T cells
Author(s) -
Bittman Robert,
Lu Xuequan,
Song Liping,
Metelitsa Leonid S.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a605-d
Subject(s) - cd1d , immune system , natural killer t cell , cytokine , chemistry , immunology , medicine , t cell
α‐Galactosylceramide (αGalCer) is recognized by mouse and human iNKT cells. We synthesized a non‐isosteric C‐αGalCer analog (α‐1C‐GalCer) in which the anomeric carbon is directly bonded to C(1) of phytoceramide. We compared the bioactivity of α‐1C‐GalCer with αGalCer and with a known isosteric C‐glycoside analog (α‐2C‐GalCer) using human dendritic cells as the antigen presenting cells and human NKT cells as the responding cells. α‐1C‐GalCer induced 2.2‐ and 8.4‐fold less IFN‐γ than that induced by α‐2C‐GalCer and αGalCer, respectively. α‐1C‐GalCer induced cytokine production with the highest ratios of both IFN‐γ/IL‐4 and IFN‐γ/IL‐13. α‐1C‐GalCer induced the least amount of another Th2 cytokine, IL‐13. These data suggest that α‐1C‐GalCer may preferentially promote Th1 immune responses. Supported in part by NIH grants HL‐083187 (to RB) and CA‐116548 (to LSM)