PMID- 21595034 OWN - NLM STAT- MEDLINE DCOM- 20110920 LR - 20230612 IS - 1615-9861 (Electronic) IS - 1615-9853 (Print) IS - 1615-9853 (Linking) VI - 11 IP - 12 DP - 2011 Jun TI - Identification and characterization of human leukocyte antigen class I ligands in renal cell carcinoma cells. PG - 2528-41 LID - 10.1002/pmic.201000486 [doi] AB - The presentation of tumor antigen-derived peptides by human leukocyte antigen (HLA) class I surface antigens on tumor cells is a key prerequisite to trigger effective T-cell responses in cancer patients. Multiple complementary strategies like cDNA and serological expression cloning, reverse immunology and different 'ome'-based methods have been employed to identify potential T-cell targets. This report focuses on a ligandomic profiling approach leading to the identification of 49 naturally processed HLA class I peptide ligands presented on the cell surface of renal cell carcinoma (RCC) cells. The source proteins of the defined HLA ligands are classified according to their biological function and subcellular localization. Previously established cDNA microarray data of paired tissue specimen of RCC and renal epithelium assessed the transcriptional regulation for 28 source proteins. In addition, HLA-A2-restricted, peptide-specific T cells directed against a HLA ligand derived from sulfiredoxin-1 (SRXN1) were generated, which were able to recognize and lyse ligand-presenting target cells in a HLA class I-restricted manner. Furthermore, tumor-infiltrating T cells isolated from a RCC patient were also able to kill SRXN1 expressing tumor cells. Thus, this experimental strategy might be suited to define potential candidate biomarkers and novel targets for T-cell-based immunotherapies of this disease. CI - Copyright (c) 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Seliger, Barbara AU - Seliger B AD - Institute of Medical Immunology, Martin-Luther University Halle-Wittenberg, Halle, Germany. barbara.seliger@medizin.uni-halle.de FAU - Dressler, Sven P AU - Dressler SP FAU - Massa, Chiara AU - Massa C FAU - Recktenwald, Christian V AU - Recktenwald CV FAU - Altenberend, Florian AU - Altenberend F FAU - Bukur, Juergen AU - Bukur J FAU - Marincola, Francesco M AU - Marincola FM FAU - Wang, Ena AU - Wang E FAU - Stevanovic, Stefan AU - Stevanovic S FAU - Lichtenfels, Rudolf AU - Lichtenfels R LA - eng GR - Z01 CL002118/ImNIH/Intramural NIH HHS/United States GR - Z01 CL002118-02/ImNIH/Intramural NIH HHS/United States GR - ZIA CL002118/ImNIH/Intramural NIH HHS/United States GR - ZIA CL002118-03/ImNIH/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110518 PL - Germany TA - Proteomics JT - Proteomics JID - 101092707 RN - 0 (Antigens, Neoplasm) RN - 0 (DNA, Complementary) RN - 0 (Epitopes) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Ligands) RN - 0 (Neoplasm Proteins) RN - EC 1.8.- (Oxidoreductases Acting on Sulfur Group Donors) RN - EC 1.8.98.2 (SRXN1 protein, human) SB - IM MH - Antigens, Neoplasm/genetics/*immunology/metabolism MH - Carcinoma, Renal Cell/genetics/*immunology/metabolism MH - Chromatography, Liquid MH - Cloning, Molecular MH - DNA, Complementary/genetics/metabolism MH - Epitopes/immunology MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic MH - Histocompatibility Antigens Class I/genetics/*immunology/metabolism MH - Humans MH - Immunotherapy/methods MH - Kidney Neoplasms/genetics/*immunology/metabolism MH - Ligands MH - Mass Spectrometry MH - Neoplasm Proteins/genetics/*immunology/metabolism MH - Oligonucleotide Array Sequence Analysis MH - Oxidoreductases Acting on Sulfur Group Donors/genetics/*immunology/metabolism MH - T-Lymphocytes, Cytotoxic/*immunology/metabolism MH - Transcription, Genetic MH - Tumor Cells, Cultured PMC - PMC3517181 MID - NIHMS421463 COIS- The authors have declared no conflict of interest. EDAT- 2011/05/20 06:00 MHDA- 2011/09/21 06:00 PMCR- 2012/12/07 CRDT- 2011/05/20 06:00 PHST- 2010/08/06 00:00 [received] PHST- 2011/03/07 00:00 [revised] PHST- 2011/03/28 00:00 [accepted] PHST- 2011/05/20 06:00 [entrez] PHST- 2011/05/20 06:00 [pubmed] PHST- 2011/09/21 06:00 [medline] PHST- 2012/12/07 00:00 [pmc-release] AID - 10.1002/pmic.201000486 [doi] PST - ppublish SO - Proteomics. 2011 Jun;11(12):2528-41. doi: 10.1002/pmic.201000486. Epub 2011 May 18.