T cell epitope definition by differential mass spectrometry: identification of a novel, immunogenic HLA-B8 ligand directly from renal cancer tissue
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chair:
Flad, T. / Müller, L. / Dihazi, H. / Grigorova, V. / Bogumil, R. / Beck, A. / Thedieck, C. / Müller, G. / Kalbacher, H. / Müller, C. (2005)
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place:
Proteomics 6 (2005), 364-374
- Date: 2005
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Flad, T. / Müller, L. / Dihazi, H. / Grigorova, V. / Bogumil, R. / Beck, A. / Thedieck, C. / Müller, G. / Kalbacher, H. / Müller, C. (2005): „T cell epitope definition by differential mass spectrometry: identification of a novel, immunogenic HLA-B8 ligand directly from renal cancer tissue”. In: Proteomics 6 (2005), 364-374
Abstract
ONLINE | |
In this study, we describe a differential mass spectrometric technique for the immuno-proteomic analysis of the major histocompatibility complex (MHC) peptides of a renal cell carcinoma (RCC) biopsy compared with the healthy kidney tissue of the same patient after nephrectomy. Using a stable isotope labeling approach, we could directly compare and relatively quantify 43 MHC-peptide pairs, most of which were present in similar proportions on both normal kidney and tumor. Significantly, two dominant peptides of monoisotopic masses [M+H]+ 973.43 u and 967.59 u, respectively, were found exclusively in the tumor sample.
One of these was identified as originating from heme oxygenase-1 (HO-1), a protein involved in induction of apoptosis resistance, immunosuppression andneoangiogenesis and reported to be up-regulated in various cancer types. Moreover, the corresponding synthetic HO-1-derived peptide was shown to be immunogenic in vitro by generation of CD8+ T cell lines with peptide-specific cytolytic activity. Thus, this peptide is an example of a differentially identified T cell epitope that could be considered as a target for immunotherapy.