T cell epitope definition by differential mass spectrometry: identification of a novel, immunogenic HLA-B8 ligand directly from renal cancer tissue

  • Autor:

    Flad, T. / Müller, L. / Dihazi, H. / Grigorova, V. / Bogumil, R. / Beck, A. / Thedieck, C. / Müller, G. / Kalbacher, H. / Müller, C. (2005)
  • Quelle:

    Proteomics 6 (2006), 1, 364–374
  • Datum: 2005

  • 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 (2006), 1, 364–374

Abstract

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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.