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T cell epitope definition by differential mass spectrometry: Identification of a novel, immunogenic HLA‐B8 ligand directly from renal cancer tissue
Author(s) -
Flad Thomas,
Mueller Ludmila,
Dihazi Hassan,
Grigorova Veneta,
Bogumil Ralf,
Beck Alexander,
Thedieck Cornelia,
Mueller Gerhard A.,
Kalbacher Hubert,
Mueller Claudia A.
Publication year - 2006
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200500099
Subject(s) - epitope , major histocompatibility complex , biology , renal cell carcinoma , peptide , cd8 , microbiology and biotechnology , immunotherapy , kidney cancer , cancer research , chemistry , antigen , immune system , immunology , biochemistry , pathology , medicine
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, immuno‐suppression and neoangiogenesis 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.