York Ian A, Mo Annie X Y, Lemerise Kristen, Zeng Wanyong, Shen Yuelei, Abraham Carmela R, Saric Tomo, Goldberg Alfred L, Rock Kenneth L
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Immunity. 2003 Mar;18(3):429-40. doi: 10.1016/s1074-7613(03)00058-x.
Most antigenic peptides presented on MHC class I molecules are generated by proteasomes during protein breakdown. It is unknown whether these peptides are protected from destruction by cytosolic peptidases. In cytosolic extracts, most antigenic peptides are degraded by the metalloendopeptidase, thimet oligopeptidase (TOP). We therefore examined whether TOP destroys antigenic peptides in vivo. When TOP was overexpressed in cells, class I presentation of antigenic peptides was reduced. In contrast, TOP overexpression didn't reduce presentation of peptides generated in the endoplasmic reticulum or endosomes. Conversely, preventing TOP expression with siRNA enhanced presentation of antigenic peptides. TOP therefore plays an important role in vivo in degrading peptides released by proteasomes and is a significant factor limiting the extent of antigen presentation.
大多数在MHC I类分子上呈递的抗原肽是在蛋白质分解过程中由蛋白酶体产生的。尚不清楚这些肽是否受到胞质肽酶的保护而不被破坏。在胞质提取物中，大多数抗原肽被金属内肽酶——硫醇寡肽酶（TOP）降解。因此，我们研究了TOP在体内是否会破坏抗原肽。当TOP在细胞中过表达时，抗原肽的I类呈递减少。相反，TOP过表达并未降低在内质网或内体中产生的肽的呈递。相反，用小干扰RNA（siRNA）阻止TOP表达可增强抗原肽的呈递。因此，TOP在体内降解蛋白酶体释放的肽中起着重要作用，并且是限制抗原呈递程度的一个重要因素。
