Pang Baoxu, Neijssen Joost, Qiao Xiaohang, Janssen Lennert, Janssen Hans, Lippuner Christoph, Neefjes Jacques
Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
J Immunol. 2009 Jul 15;183(2):1083-90. doi: 10.4049/jimmunol.0900861. Epub 2009 Jun 24.
MHC class I molecules present peptides from endogenous proteins. Ags can also be presented when derived from extracellular sources in the form of apoptotic bodies. Cross-presentation of such Ags by dendritic cells is required for proper CTL responses. The fate of Ags in cells initiated for apoptosis is unclear as is the mechanism of apoptosis-derived Ag transfer into dendritic cells. Here we show that novel Ags can be generated by caspases and be presented by MHC class I molecules of apoptotic cells. Since gap junctions function until apoptotic cells remodel to form apoptotic bodies, transfer and cross-presentation of apoptotic peptides by neighboring and dendritic cells occurs. We thus define a novel phase in classical Ag presentation and cross-presentation by MHC class I molecules: presentation of Ags created by caspase activities in cells in apoptosis.
MHC I类分子呈递内源性蛋白质来源的肽段。当抗原以凋亡小体的形式来源于细胞外时，也能够被呈递。树突状细胞对这类抗原的交叉呈递是产生适当CTL反应所必需的。细胞凋亡起始阶段抗原的命运尚不清楚，凋亡衍生抗原转移至树突状细胞的机制也不清楚。在此我们表明，半胱天冬酶能够产生新的抗原，并由凋亡细胞的MHC I类分子呈递。由于间隙连接在凋亡细胞重塑形成凋亡小体之前一直发挥作用，相邻细胞和树突状细胞可对凋亡肽进行转移和交叉呈递。因此，我们定义了MHC I类分子在经典抗原呈递和交叉呈递中的一个新的阶段：凋亡细胞中由半胱天冬酶活性产生的抗原呈递。
