| Autor: |
Hosono, Yuki, Tomiyasu, Noriyuki, Kasai, Hayato, Ishikawa, Eri, Takahashi, Masatomo, Imamura, Akihiro, Ishida, Hideharu, Compostella, Federica, Kida, Hiroshi, Kumanogoh, Atsushi, Bamba, Takeshi, Izumi, Yoshihiro, Yamasaki, Sho |
| Zdroj: |
The Journal of Experimental Medicine; February 2025, Vol. 222 Issue: 2 pe20240728-e20240728, 1p |
| Abstrakt: |
Invariant natural killer T (iNKT) cells are unconventional T cells recognizing lipid antigens in a CD1d-restricted manner. Among these lipid antigens, α-galactosylceramide (α-GalCer), which was originally identified in marine sponges, is the most potent antigen. Although the presence of α-anomeric hexosylceramide and microbiota-derived branched α-GalCer is reported, antigenic α-GalCer has not been identified in mammals. Here, we developed a high-resolution separation and detection system, supercritical fluid chromatography tandem mass spectrometry (SFC/MS/MS), that can discriminate hexosylceramide diastereomers (α-GalCer, α-GlcCer, β-GalCer, or β-GlcCer). The B16 melanoma tumor cell line does not activate iNKT cells; however, ectopic expression of CD1d was sufficient to activate iNKT cells without adding antigens. B16 melanoma was unlikely to generate iNKT cell antigens; instead, antigen activity was detected in cell culture serum. Activity-based purification and SFC/MS/MS identified dihydrosphingosine-based saturated α-GalCer as an antigenic component in serum, bile, and lymphoid tissues. These results show the first evidence for the presence of potent antigenic α-GalCer in mammals. |
| Databáze: |
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