Cancer Immunity 2:12 (2002)

Identification of a naturally processed NY-ESO-1 peptide recognized by CD8+ T cells in the context of HLA-B51

Elke Jäger¹, Julia Karbach¹, Sacha Gnjatic², Dirk Jäger¹, Markus Maeurer³, Akin Atmaca¹, Michael Arand⁴, Jonathan Skipper², Elisabeth Stockert², Yao-Tseng Chen², Lloyd J. Old², and Alexander Knuth¹

¹II. Medizinische Klinik, Hämatologie - Onkologie, Krankenhaus Nordwest, Frankfurt, Germany
²Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, USA
³Institut für Medizinische Mikrobiologie, Johannes Gutenberg Universität, Mainz, Germany
⁴Institut für Toxikologie, Johannes Gutenberg Universität, Mainz, Germany

Keywords: human, cytotoxic T lymphocytes, HLA-B51, NY-ESO-1, peptides

Abstract

NY-ESO-1 is one of the most immunogenic cancer antigens known to date, inducing humoral and cellular immune responses in a high proportion of patients with advanced NY-ESO-1-expressing cancers. The assessment of spontaneous and vaccine-induced CD8+ T cell responses has been limited to a small number of known NY-ESO-1 epitopes presented by MHC class I alleles. Recently, a new method to monitor NY-ESO-1-specific CD8+ T cell responses was introduced that does not depend on the individual MHC class I status and on predefined peptide epitopes. Antigen-presenting cells transduced with recombinant adenoviral vectors encoding NY-ESO-1 were used to stimulate CD8+ selected NY-ESO-1-specific T cells. Effector cells were tested for recognition of autologous B cell targets transfected with NY-ESO-1 using a recombinant vaccinia virus construct. Using a modified approach we identified the NY-ESO-1 p94-102 peptide as being recognized by CD8+ T cells in the context of HLA- B51. NY-ESO-1 p94-102 specific CD8+ T cells recognized naturally processed NY-ESO-1 presented by HLA-B51+ monocyte-derived dendritic and tumor cells. Transfection of target cells with NY-ESO-1 combined with different HLA class I alleles confirmed that the NY-ESO-1 peptide was naturally processed and recognized by HLA-B51-restricted CD8+ T cell lines and clones. Therefore, NY-ESO-1 p94-102 is a new candidate peptide antigen for cancer immunotherapy and for the monitoring of spontaneous and vaccine-induced NY-ESO-1-specific T cell responses in HLA- B51+ patients with NY-ESO-1 expressing malignancies.