期刊
ACS CHEMICAL BIOLOGY
卷 11, 期 12, 页码 3431-3441出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.6b00650
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资金
- Academia Sinica in Taiwan
- National Research Program for Biopharmaceuticals of the National Science Council, Taiwan [101-2325-B-001-014, 101-2325-B-001-025]
- Chang Gung Medical Foundation [OMRPG3C0013, CMRPG3D1492]
Glycosphingolipids (GSLs) bearing the agalactosyl headgroup and the acyl chain terminated with a phenyl derivative were found to be more potent than agalactosyl ceramide (alpha GalCer) to stimulate both murine and human invariant natural killer T (iNKT) cells and to induce an antibody isotope switch to IgG. In this study, we replaced the galactosyl group with glucose (alpha Glc) and its fluoro-analogs and found that phenyl GSLs with alpha Glc (C34-Glc) and its fluoro-analog 6F-C34-Glc were stronger than those with alpha Gal in stimulating human iNKT cells but weaker in mice. Their activities have a strong correlation with the binding avidities of the ternary interaction between the iNKT-cell receptor (iNKTCR) and CD1d-GSL complex. It was the iNKTCR rather than CD1d that dictated the species-specific responses. C34-Glc was further used as an adjuvant for a SSEA4-crm-197 vaccine, and after immunization in mice, the vaccine was highly effective against Lewis lung carcinoma.
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