Cancer Immunity 2:9 (2002)

Identification of a new peptide recognized by autologous cytolytic T lymphocytes on a human melanoma

Nathalie Vigneron^1,2, Annie Ooms¹, Sandra Morel², Gérard Degiovanni¹ and Benoît J. Van den Eynde²

¹Laboratory of Experimental Surgery, Tour de Pathologie, Université de Liège, Liège, Belgium
²Ludwig Institute for Cancer Research and Cellular Genetics Unit, Université de Louvain, Brussels, Belgium

Keywords: human, melanoma, cultured tumor cells, cytotoxic T lymphocytes, HLA-B44, peptide

Abstract

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.