Identification of a new peptide recognized by autologous cytolytic T lymphocytes on a human melanoma.
Melanoma line LG2-MEL expresses several antigens recognized by autologous CTLs. One of them consists of a peptide derived from tyrosinase and presented by HLA-B*3503. We have identified another antigen of LG2-MEL as a peptide presented by HLA-B*4403 and resulting from a point mutation in gene OS-9. This gene is expressed in various normal tissues. It is located on chromosome 12 in the vicinity of the CDK4 locus and is frequently co-amplified with CDK4 in human sarcomas. The mutation, a C-to-T transition, changes a proline residue into a leucine at position 446 of the OS-9 protein. Mutated transcripts were found in all the melanoma sublines of LG2-MEL. None of the 184 tumor samples collected from other cancer patients expressed the mutated transcript, indicating that this is a rare mutational event. Interestingly, some of the melanoma sublines of LG2-MEL have lost the wild-type allele of gene OS-9. Those sublines appear to grow faster in vitro than the sublines that retained the wild-type allele, suggesting that this loss of heterozygosity may favor tumor progression. The mutation we have identified in gene OS-9 might therefore participate in the oncogenic process by affecting the function of this potential tumor-suppressor gene.
Laboratory of Experimental Surgery, Tour de Pathologie, Université de Liège, Liège, Belgium.
Nathalie
N
Vigneron
Annie
A
Ooms
Sandra
S
Morel
Gérard
G
Degiovanni
Benoît J
BJ
Van Den Eynde
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D019556:COS Cells; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D018076:DNA, Complementary; D015235:HLA-B Antigens / Q000378:metabolism; D059948:HLA-B44 Antigen; D006801:Humans; D037102:Lectins; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D017354:Point Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D015235:HLA-B Antigens; D059948:HLA-B44 Antigen; D037102:Lectins; D009363:Neoplasm Proteins; C098898:OS9 protein, human; C474134:antigen LG2-C, human