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

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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

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Receptor-Like Protein Tyrosine Phosphatases
Melanoma-Specific Antigens
T-Lymphocytes
Neoplasms
Peptides
Epitopes
Immunity
Melanoma
Clone Cells
Lymph Nodes
Lymphocytes
Immunotherapy
Cytokines
Neoplasm Metastasis

ASJC Scopus subject areas

  • Immunology

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Identification of a mutated receptor-like protein tyrosine phosphatase κ as a novel, class II HLA-restricted melanoma antigen. / Novellino, Luisa; Renkvist, Nicolina; Rini, Francesca; Mazzocchi, Arabella; Rivoltini, Licia; Greco, Angela; Deho, Paola; Squarcina, Paola; Robbins, Paul F.; Parmiani, Giorgio; Castelli, Chiara.

In: Journal of Immunology, Vol. 170, No. 12, 15.06.2003, p. 6363-6370.

Research output: Contribution to journalArticle

Novellino, Luisa ; Renkvist, Nicolina ; Rini, Francesca ; Mazzocchi, Arabella ; Rivoltini, Licia ; Greco, Angela ; Deho, Paola ; Squarcina, Paola ; Robbins, Paul F. ; Parmiani, Giorgio ; Castelli, Chiara. / Identification of a mutated receptor-like protein tyrosine phosphatase κ as a novel, class II HLA-restricted melanoma antigen. In: Journal of Immunology. 2003 ; Vol. 170, No. 12. pp. 6363-6370.
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