Binder R J, Han D K, Srivastava P K
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
Nat Immunol. 2000 Aug;1(2):151-5. doi: 10.1038/77835.
Antigen presenting cells (APCs) can take up exogenous antigenic peptides chaperoned by heat shock protein gp96 and re-present them through the endogenous pathway on their major histocompatibility class I molecules. The high efficiency of this process has been attributed previously to a receptor for gp96 on APCs. The CD91 molecule (also called alpha 2-macroglobulin receptor or the low density lipoprotein-related protein) is shown here to be a cell surface receptor for the heat shock protein gp96. CD91 binds gp96 directly, rather than through another ligand for CD91. The previously known CD91 ligand, alpha 2-macroglobulin, inhibits re-presentation of gp96-chaperoned antigenic peptides by macrophages, as do antibodies to CD91. As gp96 is exclusively intracellular and is released as a result of necrotic but not apoptotic cell death, we propose that CD91 acts as a sensor for necrotic cell death.
抗原呈递细胞（APC）可以摄取由热休克蛋白gp96陪伴的外源性抗原肽，并通过内源性途径将它们重新呈递在其主要组织相容性复合体I类分子上。此前，这一过程的高效性被归因于APC上gp96的一种受体。本文显示，CD91分子（也称为α2-巨球蛋白受体或低密度脂蛋白相关蛋白）是热休克蛋白gp96的一种细胞表面受体。CD91直接结合gp96，而不是通过CD91的另一种配体。先前已知的CD91配体α2-巨球蛋白，以及针对CD91的抗体，均可抑制巨噬细胞对gp96陪伴的抗原肽的重新呈递。由于gp96仅存在于细胞内，并且是由于坏死而非凋亡性细胞死亡而释放，因此我们提出CD91作为坏死性细胞死亡的一种传感器。
