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

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Abstract

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) αβ+ 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-γ and TNF. Although lacking the CD8 molecule the gp100-specifc 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.

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Acknowledgments

We are grateful to the patient who took part in this study. We thank Jana Berger for excellent technical assistance. The authors have no conflicting financial interests.

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Authors and Affiliations

  1. Department of Internal Medicine 5, Hematology/Oncology, University of Erlangen-Nuernberg, Krankenhausstrasse 12, 91054, Erlangen, Germany

    Simon Voelkl & Andreas Mackensen

  2. Department of Hematology and Oncology, University of Regensburg, 93042, Regensburg, Germany

    Simon Voelkl, Michael Rehli, Andreas Mackensen & Karin Fischer

  3. Department of Surgery, The University of Chicago, Chicago, IL, 60637, USA

    Tamson V. Moore & Michael I. Nishimura

  4. Departments of Surgery and Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA

    Michael I. Nishimura

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  1. Simon Voelkl
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  2. Tamson V. Moore
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  4. Michael I. Nishimura
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  5. Andreas Mackensen
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  6. Karin Fischer
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Corresponding author

Correspondence to Andreas Mackensen.

Additional information

A. Mackensen and K. Fischer contributed equally to this work and should be considered joint senior authors. This work was supported by the Deutsche Forschungsgemeinschaft (MA 1351/5-1, KFO 146) and NIH grants CA90873, CA102280, 104947 (MIN).

Companion paper: “Relationship between CD8-dependent antigen recognition, T cell functional avidity, and tumor cell recognition” by Tamson V. Moore et al. doi: 10.1007/s00262-008-0594-2.

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Voelkl, S., Moore, T.V., Rehli, M. et al. Characterization of MHC class-I restricted TCRαβ+ CD4− CD8− double negative T cells recognizing the gp100 antigen from a melanoma patient after gp100 vaccination. Cancer Immunol Immunother 58, 709–718 (2009). https://doi.org/10.1007/s00262-008-0593-3

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  • DOI: https://doi.org/10.1007/s00262-008-0593-3

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