Methods and compositions are provided for reversibly localizing proteins to the exterior part of the cell surface. Compositions provided herein can include nucleic acids that encode polypeptides of interest and the ligand binding domain (LBD) of a nuclear hormone receptor. Upon addition of the ligand, the polypeptide can be localized to the extracellular side of the plasma membrane. Removal of the ligand can cause the polypeptide to be removed from the cell surface. In some embodiments, a nucleic acid construct having a LBD can be incorporated into a polypeptide having an antigen binding domain (e.g., a chimeric antigen receptor). In some embodiments, such a polypeptide can be introduced into a mammalian cell such that, upon introduction of ligand to the cell, the antigen binding domain of the polypeptide localizes to the extracellular side of the plasma membrane, and upon removal of the ligand, the antigen binding domain of the polypeptide is removed from the extracellular side of the plasma membrane. Medical applications are provided, including controlling the toxicity of CAR T cells.提供使蛋白質可逆地定位至細胞表面之外部部分之方法及組合物。本文所提供之組合物可包括編碼所關注多肽及核激素受體之配體結合域(LBD)之核酸。在添加該配體時，該多肽可定位至質膜之細胞外側。移除該配體可使該多肽自該細胞表面移除。在一些實施例中，具有LBD之核酸構築體可納入具有抗原結合域之多肽(例如嵌合抗原受體)中。在一些實施例中，可將此一多肽引入哺乳動物細胞中，使得在將配體引入該細胞時，該多肽之抗原結合域定位至該質膜之細胞外側，且在移除該配體時，該多肽之抗原結合域自該質膜之細胞外側移除。提供醫療應用，包括控制CAR T細胞之毒性。
