Identification of known and novel immunogenic T-cell epitopes from tumor antigens recognized by peripheral blood T cells from patients responding to IL-2-based treatment

• Verfasst von: Scheibenbogen, Carmen [VerfasserIn]
• Verfasst von: Song, Mingxia [VerfasserIn]
• Verfasst von: Schadendorf, Dirk [VerfasserIn]
• Titel: Identification of known and novel immunogenic T-cell epitopes from tumor antigens recognized by peripheral blood T cells from patients responding to IL-2-based treatment
• Verf.angabe: Carmen Scheibenbogen, Yuansheng Sun, Ulrich Keilholz, Mingxia Song, Stefan Stevanovic, Anne Marie Asemissen, Dirk Nagorsen, Eckhard Thiel, Hans-Georg Rammensee and Dirk Schadendorf
• E-Jahr: 2002
• Jahr: 14 January 2002
• Umfang: 6 S.
• Fussnoten: Gesehen am 11.11.2020
• Titel Quelle: Enthalten in: International journal of cancer
• Ort Quelle: Bognor Regis : Wiley-Liss, 1966
• Jahr Quelle: 2002
• Band/Heft Quelle: 98(2002), 3, Seite 409-414
• ISSN Quelle: 1097-0215
• DOI: doi:10.1002/ijc.10205
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: epitope prediction
• Sach-SW: melanoma
• Sach-SW: peptides
• Sach-SW: tyrosinase
• K10plus-PPN: 1738426327

Abstract

In previous studies CD8+ T cells specific for melanocyte antigens have been frequently found in melanoma patients responding to interleukin-2 (IL-2)-based therapies. In our study we analyzed the suitability of using circulating T cells from melanoma patients with clinical response after IL-2-based therapy to identify novel T-cell epitopes from defined tumor antigens. Using unstimulated peripheral blood mononuclear cells and the interferon-γ (IFN-γ) ELISPOT assay, we studied CD8+ T-cell responses against 5 peptides from the tumor antigen tyrosinase (Tyr) selected by epitope prediction using an HLA-A1-binding computer algorithm. T cells specifically secreting IFN-γ in response to 3 of these 5 peptides, namely, Tyr (454-463), Tyr (146-156) and Tyr (243-251), could be detected in 4 of 4 HLA-A1-positive patients with clinical response. In contrast, no T-cell responses against these peptides were seen in 6 HLA-A1-positive melanoma patients with progressive disease and in 8 healthy subjects. We could generate specific cytotoxic T lymphocytes (CTL) against Tyr (454-463) using peptide-pulsed autologous dendritic cells as antigen-presenting cells. The induced CTLs efficiently killed melanoma cells that express HLA-A1 and tyrosinase. The peptides Tyr (146-156) and Tyr (243-251) had recently been identified as CTL epitopes by other groups. Further ex vivo characterization of the T cells reactive against the novel epitope Tyr (454-463) in 1 patient by multicolor flow cytometry showed specific CD3+/CD8+/IFN-γ+ T cells with frequencies of up to 0.41% of the CD3+/CD8+ T-cell population. Most of this T-cell population also expressed granzyme B. Our data confirm that in patients with tumor regressions induced by immunotherapy or chemoimmunotherapy circulating T cells reactive with tyrosinase epitopes can frequently be detected. Peripheral blood T cells from such patients are a valuable source for screening peptides selected by epitope prediction This strategy facilitates the rapid identification of immunogenic T-cell epitopes that are probable targets of immune-mediated tumor rejection. © 2002 Wiley-Liss, Inc.