Hanada Ken-Ichi, Yewdell Jonathan W, Yang James C
Surgery Branch, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building10, Room 2B42, Bethesda, Maryland 20892, USA.
Nature. 2004 Jan 15;427(6971):252-6. doi: 10.1038/nature02240.
Cytotoxic T lymphocytes (CTLs) detect and destroy cells displaying class I molecules of the major histocompatibility complex (MHC) that present oligopeptides derived from aberrant self or foreign proteins. Most class I peptide ligands are created from proteins that are degraded by proteasomes and transported, by the transporter associated with antigen processing, from the cytosol into the endoplasmic reticulum, where peptides bind MHC class I molecules and are conveyed to the cell surface. C2 CTLs, cloned from human CTLs infiltrating a renal cell carcinoma, kill cancer cells overexpressing fibroblast growth factor-5 (FGF-5). Here we show that C2 cells recognize human leukocyte antigen-A3 MHC class I molecules presenting a nine-residue FGF-5 peptide generated by protein splicing. This process, previously described strictly in plants and unicellular organisms, entails post-translational excision of a polypeptide segment followed by ligation of the newly liberated carboxy-terminal and amino-terminal residues. The occurrence of protein splicing in vertebrates has important implications for the complexity of the vertebrate proteome and for the immune recognition of self and foreign peptides.
细胞毒性T淋巴细胞（CTL）可检测并破坏那些展示主要组织相容性复合体（MHC）I类分子的细胞，这些MHC I类分子呈递源自异常自身蛋白或外来蛋白的寡肽。大多数I类肽配体由蛋白酶体降解的蛋白质产生，并通过与抗原加工相关的转运体从胞质溶胶转运至内质网，在那里肽与MHC I类分子结合并被转运至细胞表面。从浸润肾细胞癌的人CTL中克隆出的C2 CTL可杀死过度表达成纤维细胞生长因子5（FGF-5）的癌细胞。我们在此表明，C2细胞识别呈递通过蛋白质剪接产生的九肽FGF-5肽的人白细胞抗原-A3 MHC I类分子。这一过程此前仅在植物和单细胞生物中有严格描述，需要对多肽片段进行翻译后切除，然后将新释放的羧基末端和氨基末端残基连接起来。脊椎动物中蛋白质剪接的出现对于脊椎动物蛋白质组的复杂性以及对自身和外来肽的免疫识别具有重要意义。
