Characterization of MHC class-I restricted TCRalphabeta+ CD4- CD8- double negative T cells recognizing the gp100 antigen from a melanoma patient after gp100 vaccination

Cancer Immunol Immunother. 2009 May;58(5):709-18. doi: 10.1007/s00262-008-0593-3. Epub 2008 Oct 3.


The immune attack against malignant tumors require the concerted action of CD8+ cytotoxic T lymphocytes (CTL) as well as CD4+ T helper cells. The contribution of T cell receptor (TCR) alphabeta+ CD4- CD8- double-negative (DN) T cells to anti-tumor immune responses is widely unknown. In previous studies, we have demonstrated that DN T cells with a broad TCR repertoire are present in humans in the peripheral blood and the lymph nodes of healthy individuals. Here, we characterize a human DN T cell clone (T4H2) recognizing an HLA-A2-restricted melanoma-associated antigenic gp100-peptide isolated from the peripheral blood of a melanoma patient. Antigen recognition by the T4H2 DN clone resulted in specific secretion of IFN-gamma and TNF. Although lacking the CD8 molecule the gp100-specific DN T cell clone was able to confer antigen-specific cytotoxicity against gp100-loaded target cells as well as HLA-A2+ gp100 expressing melanoma cells. The cytotoxic capacity was found to be perforin/granzymeB-dependent. Together, these data indicate that functionally active antigen-specific DN T cells recognizing MHC class I-restricted tumor-associated antigen (TAA) may contribute to anti-tumor immunity in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation
  • Antigens, CD / analysis
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Cell Line, Tumor / immunology
  • Clone Cells / immunology
  • Clone Cells / metabolism
  • Cytotoxicity, Immunologic
  • Granzymes / immunology
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunophenotyping
  • Immunotherapy, Active*
  • Interferon-gamma / metabolism
  • Interleukins / metabolism
  • Melanoma / blood
  • Melanoma / immunology*
  • Melanoma / therapy
  • Membrane Glycoproteins / immunology*
  • Perforin / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / analysis
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • gp100 Melanoma Antigen


  • Antigens, CD
  • Antigens, Neoplasm
  • Cancer Vaccines
  • HLA-A2 Antigen
  • Interleukins
  • Membrane Glycoproteins
  • PMEL protein, human
  • Receptors, Antigen, T-Cell, alpha-beta
  • Tumor Necrosis Factor-alpha
  • gp100 Melanoma Antigen
  • Perforin
  • Interferon-gamma
  • Granzymes