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

Voelkl, Simon and Moore, Tamson V. and Rehli, Michael and Nishimura, Michael I. and Mackensen, Andreas and Fischer, Karin (2009) Characterization of MHC class-I restricted TCR alpha beta(+) CD4(-) CD8(-) double negative T cells recognizing the gp100 antigen from a melanoma patient after gp100 vaccination. CANCER IMMUNOLOGY IMMUNOTHERAPY, 58 (5). pp. 709-718. ISSN 0340-7004,

Full text not available from this repository. (Request a copy)

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) alpha beta(+) 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-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.

Item Type: Article
Uncontrolled Keywords: CYTOLYTIC ACTIVITY; REGULATORY CELLS; ALPHA-3 DOMAIN; LPR MICE; RECEPTOR; RECOGNITION; MOLECULES; SELECTION; SPECIFICITY; LYMPHOCYTES; Tumor-specific T cells; DN T cells; Cancer vaccination; Tumor-associated antigen; T-cell receptor; Melanoma
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 16 Sep 2020 06:45
Last Modified: 16 Sep 2020 06:45
URI: https://pred.uni-regensburg.de/id/eprint/29007

Actions (login required)

View Item View Item