The Journal of Experimental Medicine
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Published online 1 May 2000.
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© The Rockefeller University Press, 0022-1007/2000/5/1617/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 9, May 1, 2000 1617-1624


Brief Definitive Report

A Processed Pseudogene Codes for a New Antigen Recognized by a CD8+ T Cell Clone on Melanoma

Agnès Moreau-Aubrya, Soizic Le Guinera, Nathalie Labarrièrea, Marie-Claude Gesnela, Francine Jotereaua, and Richard Breathnacha
a Institut National de la Santé et de la Recherche Médicale (INSERM) U463, 44093 Nantes cedex 01, France

Correspondence to: Richard Breathnach, INSERM U463, 9 Quai Moncousu, 44093 Nantes cedex 01, France. Tel:33-02-40-08-47-50 Fax:33-02-40-36-66-97 E-mail:breathna{at}nantes.inserm.fr.

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 from 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.

Key Words: peptide, epitope, processing, tumor immunity, CTL


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