细胞毒性T淋巴细胞相关抗原4（CTLA-4）的细胞内运输及向T细胞受体（TCR）结合位点的局灶定位

Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement.

作者信息

Linsley P S, Bradshaw J, Greene J, Peach R, Bennett K L, Mittler R S

机构信息

Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA.

出版信息

Immunity. 1996 Jun;4(6):535-43. doi: 10.1016/s1074-7613(00)80480-x.

DOI:10.1016/s1074-7613(00)80480-x

PMID:8673700

Abstract

T lymphocyte receptor CTLA-4 binds costimulatory molecules CD80 (B7-1) and CD86 (B7-2) with high avidity and negatively regulates T cell activation. CTLA-4 functions at the cell surface, yet is primarily localized in intracellular vesicles. Here, we demonstrate cycling of CTLA-4 between intracellular stores and the cell surface. Intracellular vesicles containing CTLA-4 overlapped with endocytic compartment(s) and with perforin-containing secretory granules. Cell surface expression of CTLA-4 was rapidly increased by raising intracellular calcium levels. During T cell activation, intracellular and cell surface CTLA-4 became focused towards sites of TCR activation. Cycling and directional control of CTLA-4 expression may regulate its functional interaction with APCs bearing peptide-MHC complexes of appropriate specificity and avidity.

摘要

T淋巴细胞受体CTLA-4以高亲和力结合共刺激分子CD80（B7-1）和CD86（B7-2），并对T细胞活化起负调节作用。CTLA-4在细胞表面发挥作用，但其主要定位于细胞内囊泡中。在此，我们证明了CTLA-4在细胞内储存部位和细胞表面之间的循环。含有CTLA-4的细胞内囊泡与内吞区室以及含穿孔素的分泌颗粒重叠。提高细胞内钙水平可迅速增加CTLA-4的细胞表面表达。在T细胞活化过程中，细胞内和细胞表面的CTLA-4都集中于TCR活化部位。CTLA-4表达的循环和定向控制可能调节其与带有适当特异性和亲和力的肽-MHC复合物的抗原呈递细胞的功能相互作用。