title: Identification and characterization of T-cell epitopes deduced from RGS5, a novel broadly expressed tumor antigen.
abstract: OBJECTIVE
  Identification of tumor-associated antigens and advances in tumor immunology resulted in the development of vaccination strategies to treat patients with malignant diseases. In a novel experimental approach that combined comparative mRNA expression analysis of defined cell types with the characterization of MHC ligands by mass spectrometry, we found that regulator of G protein signaling 5 (RGS5) is extensively up-regulated in a broad variety of malignant cells, and we identified two HLA-A2- and HLA-A3-binding peptides derived from the RGS5 protein. Interestingly, RGS5 was recently shown to be involved in tumor angiogenesis.
  
  
  METHODS
  We used monocyte-derived dendritic cells pulsed with these novel antigenic peptides or transfected with RGS5-mRNA for the in vitro induction of CTLs, generated from healthy donors, to analyze the presentation of RGS5-deduced epitopes by malignant cells.
  
  
  RESULTS
  The generated CTL lines elicited an antigen-specific and HLA-restricted cytolytic activity against tumor cells endogenously expressing the RGS5 protein. Furthermore, we were able to induce RGS5-specific CTLs using peripheral blood mononuclear cells from a patient with acute myeloid leukemia capable of recognizing the autologous leukemic blasts while sparing nonmalignant cells.
  
  
  CONCLUSIONS
  These results indicate that the RGS5 peptides represent interesting candidates for the development of cancer vaccines designed to target malignant cells and tumor vessels.
authors.affiliation: Department of Oncology, University of Tübingen, Tübingen, Germany.
authors.forename: Cristina N
authors.initials: CN
authors.lastname: Boss
authors.forename: Frank
authors.initials: F
authors.lastname: Grünebach
authors.forename: Katharina
authors.initials: K
authors.lastname: Brauer
authors.forename: Maik
authors.initials: M
authors.lastname: Häntschel
authors.forename: Valbona
authors.initials: V
authors.lastname: Mirakaj
authors.forename: Toni
authors.initials: T
authors.lastname: Weinschenk
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanovic
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000737:chemistry*; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry* / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic; D015789:HLA-A2 Antigen / Q000737:chemistry; D015791:HLA-A3 Antigen / Q000737:chemistry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D020710:RGS Proteins / Q000096:biosynthesis* / Q000276:immunology*; D012334:RNA, Neoplasm / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D010455:Peptides; D020710:RGS Proteins; C491349:RGS5 protein, human; D012334:RNA, Neoplasm