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A CASP-8 mutation recognized by cytolytic T lymphocytes on a human head and neck carcinoma.

Mandruzzato S, Brasseur F, Andry G, Boon T, van der Bruggen P - J. Exp. Med. (1997)

Bottom Line: The ability of the altered protein to trigger apoptosis appears to be reduced relative to the normal caspase-8.The antigenic peptide is a nonamer presented by HLA-B*3503.The five last amino acids are encoded by the extension of the reading frame caused by the mutation.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Institute for Cancer Research, Brussels Branch, and Unité de Génétique Cellulaire, Université Catholique de Louvain, B-1200 Brussels, Belgium.

ABSTRACT
Of the antigens recognized on human tumors by autologous cytolytic T lymphocytes, all those defined thus far have been identified on melanoma or renal cell carcinoma. We report here the identification of an antigen recognized by autologous cytolytic T lymphocytes on a human squamous cell carcinoma of the oral cavity. The antigen is encoded by a mutated form of the CASP-8 gene. This gene, also named FLICE or MACH, codes for protease caspase-8, which is required for induction of apoptosis through the Fas receptor and tumor necrosis factor receptor-1. The mutation, which was found in the tumor cells but not in the normal cells of the patient, modifies the stop codon and adds an Alu repeat to the coding region, thereby lengthening the protein by 88 amino acids. The ability of the altered protein to trigger apoptosis appears to be reduced relative to the normal caspase-8. The antigenic peptide is a nonamer presented by HLA-B*3503. The five last amino acids are encoded by the extension of the reading frame caused by the mutation. This, together with previous observations of CDK4 and beta-catenin mutations, suggests that a significant fraction of the point mutations generating a tumor antigen also play a role in the tumoral transformation or progression.

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Recognition of BB49-SCCHN by CTL 121 is inhibited by  anti-HLA-B,C mAb. 1,500 CTL were incubated with 20,000 BB49-SCCHN in microwells for 4 h without mAb (medium) or in the presence  of either mAb W6/32 (anti-HLA–class I), B1.23.2 (anti-HLA-B,C), BB7-2 (anti-HLA-A2), or 2B6 (anti-HLA-DR). TNF production was estimated by testing the toxicity of the supernatant for TNF-sensitive  WEHI-164.13 cells.
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Figure 2: Recognition of BB49-SCCHN by CTL 121 is inhibited by anti-HLA-B,C mAb. 1,500 CTL were incubated with 20,000 BB49-SCCHN in microwells for 4 h without mAb (medium) or in the presence of either mAb W6/32 (anti-HLA–class I), B1.23.2 (anti-HLA-B,C), BB7-2 (anti-HLA-A2), or 2B6 (anti-HLA-DR). TNF production was estimated by testing the toxicity of the supernatant for TNF-sensitive WEHI-164.13 cells.

Mentions: Patient BB49 was typed HLA-A2, -A11, -B35, -B62, -Cw01, -Cw04. CTL clone 121 secreted TNF upon stimulation with the autologous tumor cells, and TNF release was inhibited by a mAb recognizing HLA-B and HLA-C molecules. This indicates that the antigen recognized by CTL 121 is presented by HLA-B35, -B62, -Cw01, or -Cw04 (Fig. 2).


A CASP-8 mutation recognized by cytolytic T lymphocytes on a human head and neck carcinoma.

Mandruzzato S, Brasseur F, Andry G, Boon T, van der Bruggen P - J. Exp. Med. (1997)

Recognition of BB49-SCCHN by CTL 121 is inhibited by  anti-HLA-B,C mAb. 1,500 CTL were incubated with 20,000 BB49-SCCHN in microwells for 4 h without mAb (medium) or in the presence  of either mAb W6/32 (anti-HLA–class I), B1.23.2 (anti-HLA-B,C), BB7-2 (anti-HLA-A2), or 2B6 (anti-HLA-DR). TNF production was estimated by testing the toxicity of the supernatant for TNF-sensitive  WEHI-164.13 cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199018&req=5

Figure 2: Recognition of BB49-SCCHN by CTL 121 is inhibited by anti-HLA-B,C mAb. 1,500 CTL were incubated with 20,000 BB49-SCCHN in microwells for 4 h without mAb (medium) or in the presence of either mAb W6/32 (anti-HLA–class I), B1.23.2 (anti-HLA-B,C), BB7-2 (anti-HLA-A2), or 2B6 (anti-HLA-DR). TNF production was estimated by testing the toxicity of the supernatant for TNF-sensitive WEHI-164.13 cells.
Mentions: Patient BB49 was typed HLA-A2, -A11, -B35, -B62, -Cw01, -Cw04. CTL clone 121 secreted TNF upon stimulation with the autologous tumor cells, and TNF release was inhibited by a mAb recognizing HLA-B and HLA-C molecules. This indicates that the antigen recognized by CTL 121 is presented by HLA-B35, -B62, -Cw01, or -Cw04 (Fig. 2).

Bottom Line: The ability of the altered protein to trigger apoptosis appears to be reduced relative to the normal caspase-8.The antigenic peptide is a nonamer presented by HLA-B*3503.The five last amino acids are encoded by the extension of the reading frame caused by the mutation.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Institute for Cancer Research, Brussels Branch, and Unité de Génétique Cellulaire, Université Catholique de Louvain, B-1200 Brussels, Belgium.

ABSTRACT
Of the antigens recognized on human tumors by autologous cytolytic T lymphocytes, all those defined thus far have been identified on melanoma or renal cell carcinoma. We report here the identification of an antigen recognized by autologous cytolytic T lymphocytes on a human squamous cell carcinoma of the oral cavity. The antigen is encoded by a mutated form of the CASP-8 gene. This gene, also named FLICE or MACH, codes for protease caspase-8, which is required for induction of apoptosis through the Fas receptor and tumor necrosis factor receptor-1. The mutation, which was found in the tumor cells but not in the normal cells of the patient, modifies the stop codon and adds an Alu repeat to the coding region, thereby lengthening the protein by 88 amino acids. The ability of the altered protein to trigger apoptosis appears to be reduced relative to the normal caspase-8. The antigenic peptide is a nonamer presented by HLA-B*3503. The five last amino acids are encoded by the extension of the reading frame caused by the mutation. This, together with previous observations of CDK4 and beta-catenin mutations, suggests that a significant fraction of the point mutations generating a tumor antigen also play a role in the tumoral transformation or progression.

Show MeSH
Related in: MedlinePlus