A processed pseudogene codes for a new antigen recognized by a CD8(+) T cell clone on melanoma.
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.
Moreau-Aubry
A
A
Institut National de la Santé et de la Recherche Médicale (INSERM) U463, 44093 Nantes cedex 01, France.
Le Guiner
S
S
Labarrière
N
N
Gesnel
M C
MC
Jotereau
F
F
Breathnach
R
R
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000235:genetics*; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D018388:Codon, Terminator; D003602:Cytotoxicity, Immunologic; D015723:Gene Library; D015235:HLA-B Antigens / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011544:Pseudogenes; D012689:Sequence Homology, Nucleic Acid
D000951:Antigens, Neoplasm; D018388:Codon, Terminator; D015235:HLA-B Antigens; D018398:Homeodomain Proteins; C408345:NA88-A antigen; D010446:Peptide Fragments; C408346:VENTX protein, human