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*
Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, University Hospital, Lausanne, Switzerland;
Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany;
Medizinische Klinik I, Universität des Saarlandes, Homburg, Germany; and
Ludwig Institute for Cancer Research, Lausanne Branch, and
¶ Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland
The tumor Ag SSX-2 (HOM-MEL-40) was found by serological identification of Ags by recombinant expression cloning and was shown to be a cancer/testis Ag expressed in a wide variety of tumors. It may therefore represent a source of CD8+ T cell epitopes useful for specific immunotherapy of cancer. To identify potential SSX-2-derived epitopes that can be recognized by CD8+ T cells, we used an approach that combined: 1) the in vitro proteasomal digestion of precursor peptides overlapping the complete SSX-2 sequence; 2) the prediction of SSX-2-derived peptides with an appropriate HLA-A2 binding score; and 3) the analysis of a tumor-infiltrated lymph node cell population from an HLA-A2+ melanoma patient with detectable anti-SSX-2 serum Abs. This strategy allowed us to identify peptide SSX-241–49 as an HLA-A2-restricted epitope. SSX241–49-specific CD8+ T cells were readily detectable in the tumor-infiltrated lymph node population by multimer staining, and CTL clones isolated by multimer-guided cell sorting were able to lyse HLA-A2+ tumor cells expressing SSX-2.
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