Saposin C is required for lipid presentation by human CD1b

被引：141

作者：

Winau, F

Schwierzeck, V

Hurwitz, R

Remmel, N

Sieling, PA

Modlin, RL

Porcelli, SA

Brinkmann, V

Sugita, M

Sandhoff, K

Kaufmann, SHE

Schaible, UE

机构：

[1] Max Planck Inst Infect Biol, Dept Immunol, D-10117 Berlin, Germany

[2] Max Planck Inst Infect Biol, Cent Core Facil Prot Biochem, D-10117 Berlin, Germany

[3] Kekule Inst Organ Chem & Biochem, D-53121 Bonn, Germany

[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Dermatol, Los Angeles, CA 90095 USA

[5] Albert Einstein Coll Med, Dept Microbiol & Immunol, New York, NY 10461 USA

[6] Max Planck Inst Infect Biol, Cent Core Facil Microscopy, D-10117 Berlin, Germany

[7] Nippon Med Coll, Dept Microbiol & Immunol, Bunkyo Ku, Tokyo 1138602, Japan

来源：

NATURE IMMUNOLOGY | 2004年 / 5卷 / 02期

关键词：

D O I：

10.1038/ni1035

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Lipids from Mycobacterium tuberculosis are presented through CD1 proteins to T lymphocytes in humans, but the accessory molecules required for antigen loading and presentation remain unidentified. Here we show that fibroblasts deficient in sphingolipid activator proteins (SAPs) transfected with CD1b failed to activate lipid-specific T cells. However, the T cell response was restored when fibroblasts were reconstituted with SAP-C but not other SAPs. Lipid antigen and SAP-C colocalized in lysosomal compartments, and liposome assays showed that SAP-C efficiently extracts antigen from membranes. Coprecipitation demonstrated direct molecular interaction between SAP-C and CD1b. We propose a model in which SAP-C exposes lipid antigens from intralysosomal membranes for loading onto CD1b. Thus, SAP-C represents a missing link in antigen presentation of lipids through CD1b to human T cells.

引用

页码：169 / 174

页数：6

共 34 条

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