title: Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy.
abstract: Alterations in phosphorylation of cellular proteins are a hallmark of malignant transformation. Degradation of these phosphoproteins could generate cancer-specific class I MHC-associated phosphopeptides recognizable by CD8+ T lymphocytes. In a comparative analysis of phosphopeptides presented on the surface of melanoma, ovarian carcinoma, and B lymphoblastoid cells, we find 5 of 36 that are restricted to the solid tumors and common to both cancers. Differential presentation of these peptides can result from differential phosphorylation of the source proteins. Recognition of the peptides on cancer cells by phosphopeptide-specific CD8+ T lymphocytes validates the potential of these phosphopeptides as immunotherapeutic targets.
authors.affiliation: Beirne B. Carter Immunology Center and Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Zarling
authors.forename: Joy M
authors.initials: JM
authors.lastname: Polefrone
authors.forename: Anne M
authors.initials: AM
authors.lastname: Evans
authors.forename: Leann M
authors.initials: LM
authors.lastname: Mikesh
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Shabanowitz
authors.forename: Sarah T
authors.initials: ST
authors.lastname: Lewis
authors.forename: Victor H
authors.initials: VH
authors.lastname: Engelhard
authors.forename: Donald F
authors.initials: DF
authors.lastname: Hunt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D000939:Epitopes / Q000276:immunology; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D010748:Phosphopeptides / Q000737:chemistry / Q000276:immunology*; D010750:Phosphoproteins / Q000276:immunology; D010766:Phosphorylation; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000939:Epitopes; D015789:HLA-A2 Antigen; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526298:Irs2 protein, mouse; D009363:Neoplasm Proteins; D010748:Phosphopeptides; D010750:Phosphoproteins