Lysosomal recycling terminates CD1d-mediated presentation of short and polyunsaturated variants of the NKT cell lipid antigen alpha GalCer

Bai L; Sagiv Y; Liu YFreigang SYu KOATeyton LPorcelli SASavage PBBendelac A

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Lysosomal recycling terminates CD1d-mediated presentation of short and polyunsaturated variants of the NKT cell lipid antigen alpha GalCer

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Short or polyunsaturated lipid variants of the NKT cell antigen alpha-galactosylceramide (alpha GC) exhibit decreased potency and a Th2 bias in vivo despite conserved TCR contact residues and stable binding to CD1d at neutral and acidic pH. Using reagents to directly visualize lipids in their free or CD1d-bound form, we determined that, contrary to predictions, these lipids reached the lysosome better than alpha GC. However, in contrast with alpha GC, they loaded CD1d at the cell surface and underwent immediate pH-dependent dissociation upon recycling to the lysosome. In cell-free assays, ultrafast dissociation of preformed complexes could be induced at acidic pH only when free competitor lipids were added, suggesting active lipid displacement. These findings provide a common cell biological explanation for the decreased stimulatory properties of short and polyunsaturated alpha GC variants. They also suggest that direct lipid displacement is a potent mechanism underlying highly dynamic lipid exchange reactions in the lysosomal compartment that shape the repertoire of lipids associated with CD1d.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2009年第25期|10254-10259|共6页
作者
Bai L; Sagiv Y; Liu YFreigang SYu KOATeyton LPorcelli SASavage PBBendelac A;
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作者单位

Howard Hughes Medical Institute, Committee on Immunology, Department of Pathology, University of Chicago, Chicago, IL 60637;

Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602;

Department of Immunology, Scripps Research Institute, La Jolla, CA 92037Department of Microbiology and Immunology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
recycling; variants; lysosome;

Lysosomal recycling terminates CD1d-mediated presentation of short and polyunsaturated variants of the NKT cell lipid antigen alpha GalCer

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