Noessner, Elfriede and Gastpar, Robert and Milani, Valeria and Brandl, Anna and Hutzler, Peter J. S. and Kuppner, Maria C. and Roos, Miriam and Kremmer, Elisabeth and Asea, Alexzander and Calderwood, Stuart K. and Issels, Rolf D. (2002) Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells. JOURNAL OF IMMUNOLOGY, 169 (10). pp. 5424-5432. ISSN 0022-1767
Full text not available from this repository. (Request a copy)Abstract
Our study demonstrates that tumor-derived heat shock protein (HSP)70 chaperones a tyrosinase peptide and mediates its transfer to human immature dendritic cells (DCs) by receptor-dependent uptake. Human tumor-derived HSP70 peptide complexes (HSP70-PC) thus have the immunogenic potential to instruct DCs to cross-present endogenously expressed, nonmutated, and tumor antigenic peptides that are shared among tumors of the melanocytic lineage for T cell recognition. T cell stimulation by HSP70-instructed DCs is dependent on the Ag bound to HSP70 in that only DCs incubated with HSP70-PC purified from tyrosinase-positive (HSP70-PC/tyr(+)) but not from tyrosinase-negative (HSP70-PC/tyr(-)) melanoma cells resulted in the specific activation of the HLA-A*0201-restricted tyrosinase peptide-specific cytotoxic T cell clone. HSP70-PC-mediated T cell stimulation is very efficient, delivering the tyrosinase peptide at concentrations as low as 30 ng/ml of HSP70-PC for T cell recognition. Receptor-dependent binding of HSP70-PC and active cell metabolism are prerequisites for MHC class I-restricted cross-presentation and T cell stimulation. T cell stimulation does not require external DC maturation signals (e.g., exogenously added TNF-alpha), suggesting that signaling DC maturation is an intrinsic property of the HSP70-PC itself and related to receptor-mediated binding. The cross-presentation of a shared human tumor Ag together with the exquisite efficacy are important new aspects for HSP70-based immunotherapy in clinical anti-cancer vaccination strategies, and suggest a potential extension of HSP70-based vaccination protocols from a patient-individual treatment modality to its use in an allogeneic setting.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CYTOTOXIC T-LYMPHOCYTES; RECEPTOR-MEDIATED ENDOCYTOSIS; GP96 INDUCES MATURATION; NATURAL-KILLER-CELLS; MELANOMA-CELLS; CUTTING EDGE; IN-VIVO; CHAPERONED PEPTIDES; ANTITUMOR IMMUNITY; STRESS PROTEINS; |
| 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: | 29 Sep 2021 05:21 |
| Last Modified: | 29 Sep 2021 05:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/39666 |
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