Characterization of MHC class-I restricted TCRalphabeta+ CD4- CD8- double negative T cells recognizing the gp100 antigen from a melanoma patient after gp100 vaccination.
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.
Department of Internal Medicine 5, Hematology/Oncology, University of Erlangen-Nuernberg, Krankenhausstrasse 12, Erlangen, Germany.
Simon
S
Voelkl
Tamson V
TV
Moore
Michael
M
Rehli
Michael I
MI
Nishimura
Andreas
A
Mackensen
Karin
K
Fischer
D017951:Antigen Presentation; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000276:immunology; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D053804:Granzymes / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016233:Immunotherapy, Active; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008545:Melanoma / Q000097:blood / Q000276:immunology* / Q000628:therapy; D008562:Membrane Glycoproteins / Q000276:immunology*; D054353:Perforin / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D058951:gp100 Melanoma Antigen
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D007378:Interleukins; D008562:Membrane Glycoproteins; C548637:PMEL protein, human; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D058951:gp100 Melanoma Antigen; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes