Multiple Melanoma-Associated Epitopes Recognized by HLA-A3-Restricted CTLs and Shared by Melanomas but Not Melanocytes

Arabella Mazzocchi, Walter J. Storkus, Catia Traversari, Paolo Tarsini, Markus J. Maeurer, Licia Rivoltini, Claudia Vegetti, Filiberto Belli, Andrea Anichini, Giorgio Parmiani, Chiara Castelli

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Abstract

The molecular characterization of melanoma-associated Ags allowed the definition of several HLA class I-presented peptides recognized by T cells. However, no HLA-A3.1-restricted melanoma epitopes have been identified to date. To gain insight into the HLA-A3.1-restricted T cell epitope repertoire of human melanoma, we analyzed the immunologic reactivity of CTLs isolated from tumor-involved or tumor-free lymph nodes in two HLA-A3.1+ melanoma patients. Three CTL lines, clonal or highly oligoclonal in their TCR composition, and two CTL clones were selected for HLA class I-restricted lysis of the autologous tumor and then tested for the recognition of HLA-A3+ and HLA-A3- normal or neoplastic cells of the melanocyte lineage. One CTL recognized a unique HLA-A3.1-restricted Ag expressed only by the autologous tumors, while all the other CTLs defined three HLA-A3.1 epitopes shared by melanomas, but not by melanocytes. Moreover, the epitopes of two CTL lines with different specificity were reconstituted by nonoverlapping fractions of HLA-A3+ melanoma-derived peptides resolved by reverse phase-HPLC, indicating that distinct naturally processed peptides were specifically recognized on melanoma cells in association with HLA-A3.1 molecules. These novel lineage-unrelated HLA-A3.1-restricted melanoma epitopes do not derive from MAGE, BAGE, or GAGE gene families, as evaluated by the COS-7 transfection assay. Our data show that CTLs may recognize HLA-A3.1-class I complexes presenting melanoma (but not melanocyte)-associated epitopes that are either unique to a given patient's tumor or that are shared between multiple melanomas.

Original languageEnglish
Pages (from-to)3030-3038
Number of pages9
JournalJournal of Immunology
Volume157
Issue number7
Publication statusPublished - Oct 1 1996

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ASJC Scopus subject areas

  • Immunology

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