A processed pseudogene codes for a new antigen recognized by a CD8(+) T cell clone on melanoma. NLM AIDSLINE Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

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

J Exp Med. 2000 May 1;191(9):1617-24. Unique Identifier : AIDSLINE GENBANK/AF164963
Moreau-Aubry A; Le Guiner S; Labarriere N; Gesnel MC; Jotereau F; Breathnach R; Institut National de la Sante et de la Recherche Medicale; (INSERM) U463, 44093 Nantes cedex 01, France.

Abstract: 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.

Keywords: JOURNAL ARTICLE Amino Acid Sequence Antigen Presentation Antigens, Neoplasm/*GENETICS Base Sequence Clone Cells/IMMUNOLOGY Codon, Terminator *Cytotoxicity, Immunologic CD8-Positive T-Lymphocytes/*IMMUNOLOGY Gene Library Homeodomain Proteins/*GENETICS/IMMUNOLOGY Human HLA-B Antigens/IMMUNOLOGY Lymphocyte Transformation/GENETICS Melanoma/GENETICS/*IMMUNOLOGY Molecular Sequence Data Peptide Fragments/IMMUNOLOGY *Pseudogenes Sequence Homology, Nucleic Acid Support, Non-U.S. Gov't

KWDjournalarticleaminoacidsequenceantigenpresentationantigens,neoplasm/KWDgeneticsbasesequenceclonecells/immunologycodon,terminatorKWDcytotoxicity,immunologiccd8-positivet-lymphocytes/KWDimmunologygenelibraryhomeodomainproteins/KWDgenetics/immunologyhumanhla-bantigens/immunologylymphocytetransformation/geneticsmelanoma/genetics/KWDimmunologymolecularsequencedatapeptidefragments/immunologyKWDpseudogenessequencehomology,nucleicacidsupport,non-uKWDsKWDgov't
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