Identification of a mutated receptor-like protein tyrosine phosphatase κ as a novel, class II HLA-restricted melanoma antigen

Luisa Novellino, Nicolina Renkvist, Francesca Rini, Arabella Mazzocchi, Licia Rivoltini, Angela Greco, Paola Deho, Paola Squarcina, Paul F. Robbins, Giorgio Parmiani, Chiara Castelli

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies increasingly point to a pivotal role of CD4 + T cells in human anti-tumor immune response. Here we show that lymphocytes purified from a tumor-infiltrated lymph node of a melanoma patient that had remained disease free for 10 years after surgical resection of a lymph node metastasis comprised oligoclonal class II HLA-restricted CD4 + T cells recognizing the autologous tumor cells in vitro. In fact, the CD4 + T cell clones isolated from these lymphocytes displayed a tumor-specific, cytotoxic activity in addition to a Th1-like cytokine profile. By a genetic approach, a peptide derived from a mutated receptor-like protein tyrosine phosphatase κ was identified as a novel HLA-DR10-restricted epitope for all the melanoma-specific CD4 + T cell clones. The immunogenic peptide was shown to contain the mutated residue that was crucial for T cell recognition and activation. Moreover, a systemic immunity against the mutated peptide was detectable in the patient's peripheral blood T lymphocytes obtained during the disease-free period of follow-up. These findings further support the relevance of CD4 + T cells directed against mutated epitopes in tumor immunity and provide the rationale for a possible usage of mutated, tumor-specific Ags for immunotherapy of human cancer.

Original languageEnglish
Pages (from-to)6363-6370
Number of pages8
JournalJournal of Immunology
Volume170
Issue number12
Publication statusPublished - Jun 15 2003

ASJC Scopus subject areas

  • Immunology

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