Phenyl Glycolipids with Different Glycosyl Groups Exhibit Marked Differences in Murine and Human iNKT Cell Activation

Tai Na Wu; Kun Hsien Lin; Ying Ta Wu; Jing Rong Huang; Jung Tung Hung; Jen Chine Wu; Chien Yu Chen; Kuo Ching Chu; Nan Horng Lin; Alice L. Yu; Chi Huey Wong

doi:10.1021/acschembio.6b00650

Phenyl Glycolipids with Different Glycosyl Groups Exhibit Marked Differences in Murine and Human iNKT Cell Activation

Tai Na Wu, Kun Hsien Lin, Ying Ta Wu, Jing Rong Huang, Jung Tung Hung, Jen Chine Wu, Chien Yu Chen, Kuo Ching Chu, Nan Horng Lin, Alice L. Yu^*, Chi Huey Wong

^*Corresponding author for this work

Graduate Institute of Biomedical Sciences

Research output: Contribution to journal › Journal Article › peer-review

12 Scopus citations

Abstract

Glycosphingolipids (GSLs) bearing the α-galactosyl headgroup and the acyl chain terminated with a phenyl derivative were found to be more potent than α-galactosyl ceramide (αGalCer) 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 (αGlc) and its fluoro-analogs and found that phenyl GSLs with αGlc (C34-Glc) and its fluoro-analog 6F-C34-Glc were stronger than those with αGal 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.

Original language	English
Pages (from-to)	3431-3441
Number of pages	11
Journal	ACS Chemical Biology
Volume	11
Issue number	12
DOIs	https://doi.org/10.1021/acschembio.6b00650
State	Published - 16 12 2016

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© 2016 American Chemical Society.

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title = "Phenyl Glycolipids with Different Glycosyl Groups Exhibit Marked Differences in Murine and Human iNKT Cell Activation",

abstract = "Glycosphingolipids (GSLs) bearing the α-galactosyl headgroup and the acyl chain terminated with a phenyl derivative were found to be more potent than α-galactosyl ceramide (αGalCer) 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 (αGlc) and its fluoro-analogs and found that phenyl GSLs with αGlc (C34-Glc) and its fluoro-analog 6F-C34-Glc were stronger than those with αGal 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.",

author = "Wu, {Tai Na} and Lin, {Kun Hsien} and Wu, {Ying Ta} and Huang, {Jing Rong} and Hung, {Jung Tung} and Wu, {Jen Chine} and Chen, {Chien Yu} and Chu, {Kuo Ching} and Lin, {Nan Horng} and Yu, {Alice L.} and Wong, {Chi Huey}",

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year = "2016",

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doi = "10.1021/acschembio.6b00650",

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AU - Wu, Tai Na

AU - Lin, Kun Hsien

AU - Wu, Ying Ta

AU - Huang, Jing Rong

AU - Hung, Jung Tung

AU - Wu, Jen Chine

AU - Chen, Chien Yu

AU - Chu, Kuo Ching

AU - Lin, Nan Horng

AU - Yu, Alice L.

AU - Wong, Chi Huey

PY - 2016/12/16

Y1 - 2016/12/16

N2 - Glycosphingolipids (GSLs) bearing the α-galactosyl headgroup and the acyl chain terminated with a phenyl derivative were found to be more potent than α-galactosyl ceramide (αGalCer) 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 (αGlc) and its fluoro-analogs and found that phenyl GSLs with αGlc (C34-Glc) and its fluoro-analog 6F-C34-Glc were stronger than those with αGal 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.

AB - Glycosphingolipids (GSLs) bearing the α-galactosyl headgroup and the acyl chain terminated with a phenyl derivative were found to be more potent than α-galactosyl ceramide (αGalCer) 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 (αGlc) and its fluoro-analogs and found that phenyl GSLs with αGlc (C34-Glc) and its fluoro-analog 6F-C34-Glc were stronger than those with αGal 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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Phenyl Glycolipids with Different Glycosyl Groups Exhibit Marked Differences in Murine and Human iNKT Cell Activation

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