Translocation of CD28 to lipid rafts and costimulation of IL-2

被引:22
作者
Sadra, A
Cinek, T
Imboden, JB [1 ]
机构
[1] San Francisco Gen Hosp, Rosalind Russell Res Lab, Dept Med, San Francisco, CA 94110 USA
[2] Univ Calif San Francisco, San Francisco, CA 94143 USA
关键词
D O I
10.1073/pnas.0403792101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Stimulation of the CD28 costimulatory receptor can lead to an increased surface lipid raft expression in T lymphocytes. Here, we demonstrate that CD28 itself is recruited to lipid rafts in both Jurkat and peripheral blood T lymphocytes. This recruitment of CD28 is triggered by engagement with either anti-CD28 mAbs or a natural ligand of CD28, B7.2 (CD86). All detectable tyrosine-phosphorylated CD28 is in the lipid raft fractions, as is all of the CD28 associated with phosphatidylinositol 3-kinase, which is recruited to CD28 by tyrosine phosphorylation. Targeting the CD28 cytoplasmic domain to lipid rafts results in its tyrosine phosphorylation, indicating that tyrosine phosphorylation of CD28 may occur after translocation to lipid rafts. Studies with Jurkat cells deficient in Lck and CD45 demonstrate that movement of CD28 into lipid rafts does not require Lck and CD45 and can occur despite reduction of CD28 tyrosine phosphorylation to below the levels of detection. Analysis of murine CD28 mutants reveals a correlation between translocation to lipid rafts and costimulation of IL-2 production. Taken together with the known importance of lipid rafts in T cell activation, these observations suggest that translocation to lipid rafts may play an important role in CD28 signaling.
引用
收藏
页码:11422 / 11427
页数:6
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