Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4357-64. doi: 10.1073/pnas.1200764109. Epub 2012 Feb 13.
Transferring lipid antigens from membranes into CD1 antigen-presenting proteins represents a major molecular hurdle necessary for T-cell recognition. Saposins facilitate this process, but the mechanisms used are not well understood. We found that saposin B forms soluble saposin protein-lipid complexes detected by native gel electrophoresis that can directly load CD1 proteins. Because saposin B must bind lipids directly to function, we found it could not accommodate long acyl chain containing lipids. In contrast, saposin C facilitates CD1 lipid loading in a different way. It uses a stable, membrane-associated topology and was capable of loading lipid antigens without forming soluble saposin-lipid antigen complexes. These findings reveal how saposins use different strategies to facilitate transfer of structurally diverse lipid antigens.
将脂质抗原从膜转移到 CD1 抗原呈递蛋白代表了 T 细胞识别所必需的主要分子障碍。类脂运载蛋白促进了这一过程，但使用的机制尚不清楚。我们发现，SAPO 蛋白 B 形成可通过天然凝胶电泳检测到的可溶性 SAPO 蛋白-脂质复合物，可直接负载 CD1 蛋白。由于 SAPO 蛋白 B 必须直接结合脂质才能发挥作用，因此我们发现它不能容纳含有长酰基链的脂质。相比之下，SAPO 蛋白 C 以不同的方式促进 CD1 脂质加载。它使用稳定的、与膜相关的拓扑结构，能够加载脂质抗原而不形成可溶性 SAPO 蛋白-脂质抗原复合物。这些发现揭示了 SAPO 蛋白如何使用不同的策略来促进结构多样的脂质抗原的转移。
