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Identification of a mutated receptor-like protein tyrosine phosphatase κ as a novel, class II HLA-restricted melanoma antigen
- Source :
- Scopus-Elsevier
-
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.
- Subjects :
- CD4-Positive T-Lymphocytes
medicine.medical_treatment
T cell
Immunology
Molecular Sequence Data
Epitopes, T-Lymphocyte
Human leukocyte antigen
Biology
Transfection
Epitope
Interleukin 21
Immune system
Lymphocytes, Tumor-Infiltrating
Antigens, Neoplasm
medicine
Tumor Cells, Cultured
Immunology and Allergy
Cytotoxic T cell
Humans
IL-2 receptor
Amino Acid Sequence
RNA, Messenger
Melanoma
Cell Line, Transformed
Antigen Presentation
Histocompatibility Antigens Class II
Receptor-Like Protein Tyrosine Phosphatases, Class 2
Immunotherapy
HLA-DR Antigens
Molecular biology
Peptide Fragments
Clone Cells
Antigens, Differentiation, B-Lymphocyte
medicine.anatomical_structure
Mutation
Protein Tyrosine Phosphatases
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Scopus-Elsevier
- Accession number :
- edsair.doi.dedup.....3f1bf22d25cc6e3227b3424186cd2c26