A processed pseudogene codes for a new antigen recognized by a CD8+ T cell clone on melanoma

被引:56
作者
Moreau-Aubry, A [1 ]
Le Guiner, S [1 ]
Labarrière, N [1 ]
Gesnel, MC [1 ]
Jotereau, F [1 ]
Breathnach, R [1 ]
机构
[1] INSERM, U463, F-44093 Nantes 01, France
关键词
peptide; epitope; processing; tumor immunity; CTL;
D O I
10.1084/jem.191.9.1617
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The M88.7 T cell clone recognizes an antigen presented by HLA B*1302 on the melanoma cell line M88. A cDNA encoding this antigen (NA88-A) was isolated using a library transfection approach. Analysis of the genomic gene's sequence identified it is a processed pseudogene, derived from a retrotranscript of mRNA coding for homeoprotein HPX42B. The NA88-A gene exhibits several premature stop codons, deletions, and insertions relative to the HPX42B gene. In NA88-A RNA, a short open reading frame codes for the peptide MTQGQHFLQKV front which antigenic peptides are derived; a stop codon follows the peptide's COOH-terminal Val codon. Part of the HPX42B mRNA's 3' untranslated region codes for a peptide of similar sequence (MTQGQHFSQKV). If produced, this peptide can be recognized by M88.7 T cells. However, in HPX42B mRNA, the peptide's COOH-terminal Val codon is followed by a Trp codon. As a result, expression of HPX42B mRNA does not lead to antigen production. A model is proposed for events that participated in creation of a gene coding for a melanoma antigen from a pseudogene.
引用
收藏
页码:1617 / 1623
页数:7
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