| Autor: |
J L, Vissers, I J, De Vries, M W, Schreurs, L P, Engelen, E, Oosterwijk, C G, Figdor, G J, Adema |
| Rok vydání: |
1999 |
| Předmět: |
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| Zdroj: |
Cancer research. 59(21) |
| ISSN: |
0008-5472 |
| Popis: |
Evidence has accumulated that the immune system can play a significant role in the defense against tumors in humans. Especially melanoma and renal cell carcinoma (RCC) are considered immunogenic tumors. In contrast to melanoma, hardly any RCC-associated antigens have been identified as targets for RCC-reactive T cells. Here, we report the identification of a human leukocyte antigen (HLA)-A2.1-restricted T-cell epitope within the G250 antigen. This antigen is expressed in 85% of RCCs but not by neighboring normal kidney tissue and has recently been molecularly defined and shown to be identical to MN/CA IX. Computer-aided motif prediction revealed the presence of 60 potential HLA-A2.1-binding peptides within the G250 antigen. Subsequent binding analysis showed that 13 of these peptides bound to HLA-A2.1 with high-to-intermediate affinity. Analysis of their immunogenicity in HLA-A2.1Kb transgenic mice indicated that 4 of the 13 peptides gave rise to cytotoxic T lymphocytes (CTLs) capable of lysing peptide-loaded target cells. However, only the G250 peptide 254-262 induced CTLs that recognized target cells that endogenously expressed the G250 antigen. Similarly, we were also able to raise human CTLs against the G250 peptide 254-262, which lysed target cells that endogenously expressed the G250 antigen. These findings and the high prevalence of this antigen in RCC patients makes G250 a potential target for anti-RCC immunotherapy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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