Immune recognition of a human renal cancer antigen through post-translational protein splicing

被引:256
作者
Hanada, K
Yewdell, JW
Yang, JC
机构
[1] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA
[2] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA
基金
英国生物技术与生命科学研究理事会; 英国工程与自然科学研究理事会; 英国惠康基金;
关键词
D O I
10.1038/nature02240
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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(1). C2 CTLs, cloned from human CTLs infiltrating a renal cell carcinoma, kill cancer cells overexpressing fibroblast growth factor-5 (FGF-5)(2). 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(3) and unicellular organisms(4), entails post-translational excision of a polypeptide segment followed by ligation of the newly liberated carboxyterminal 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.
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页码:252 / 256
页数:5
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