A new LAGE-1 peptide recognized by cytolytic T lymphocytes on HLA-A68 tumors.
Antigens encoded by genes of the LAGE family, including LAGE-1 and NY-ESO-1, are of interest for cancer immunotherapy because they are tumor-specific and shared by tumors of different histological types. Several clinical trials are in progress with NY-ESO-1 peptides, protein, recombinant poxviruses, and dendritic cells pulsed with peptides. In this study, CD8 T lymphocytes from an individual without cancer were stimulated with dendritic cells infected with a recombinant avian poxvirus encoding a complete LAGE-1 protein. A CTL clone was isolated that recognized a new LAGE-1 peptide, ELVRRILSR, which corresponds to position 103-111 of the protein sequence. It is presented by HLA-A6801 molecules. When tumor cells expressing LAGE-1 were transfected with HLA-A68, they were lysed by the CTL clone, indicating that the peptide is processed in tumor cells. These results indicate that the LAGE-1.A68 peptide can be used for antitumoral vaccination. We observed also that specific T cells could be detected in a blood sample with a high sensitivity by using an A68/LAGE-1 fluorescent multimer.
Sun
Zhaojun
Z
Ludwig Institute for Cancer Research Institute of Cellular Pathology, Cellular Genetics Unit, Université de Louvain, 74 avenue Hippocrate, UCL 7459, 1200, Brussels, Belgium.
Lethé
Bernard
B
Zhang
Yi
Y
Russo
Vincenzo
V
Colau
Didier
D
Stroobant
Vincent
V
Boon
Thierry
T
van der Bruggen
Pierre
P
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface; D019556:COS Cells; D002522:Chlorocebus aethiops; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008545:Melanoma / Q000276:immunology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C104948:CTAG1B protein, human; C510162:CTAG2 protein, human; D006680:HLA Antigens; D008565:Membrane Proteins; D010455:Peptides