Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy.
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.
Zarling
Angela L
AL
Beirne B. Carter Immunology Center and Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
Polefrone
Joy M
JM
Evans
Anne M
AM
Mikesh
Leann M
LM
Shabanowitz
Jeffrey
J
Lewis
Sarah T
ST
Engelhard
Victor H
VH
Hunt
Donald F
DF
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
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