HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fleischer, K. Articles by Bernhard, H. Search for Related Content PubMed PubMed Citation Articles by Fleischer, K. Articles by Bernhard, H. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Melanoma

Melanoma-Reactive Class I-Restricted Cytotoxic T Cell Clones Are Stimulated by Dendritic Cells Loaded with Synthetic Peptides, but Fail to Respond to Dendritic Cells Pulsed with Melanoma-Derived Heat Shock Proteins In Vitro¹

Kristina Fleischer^2,*, Burkhard Schmidt^2,*, Wolfgang Kastenmüller^*, Dirk H. Busch, Ingo Drexler, Gerd Sutter, Michael Heike, Christian Peschel^* and Helga Bernhard^3,*

Departments of ^* Hematology/Oncology, Microbiology and Immunology, and Virology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany; and Department of Gastroenterology, University of Mainz, Mainz, Germany

Immunization with heat shock proteins (hsp) isolated from cancer cells has been shown to induce a protective antitumor response. The mechanism of hsp-dependent cellular immunity has been attributed to a variety of immunological activities mediated by hsp. Hsp have been shown to bind antigenic peptides, trim the bound peptides by intrinsic enzymatic activity, improve endocytosis of the chaperoned peptides by APCs, and enhance the ability of APCs to stimulate peptide-specific T cells. We have investigated the potential capacity of hsp70 and gp96 to function as a mediator for Ag-specific CTL stimulation in an in vitro model for human melanoma. Repetitive stimulation of PBLs by autologous DCs loaded with melanoma-derived hsp did not increase the frequency of T cells directed against immunodominant peptides of melanoma-associated Ags Melan-A and tyrosinase. In contrast, repeated T cell stimulation with peptide-pulsed DCs enhanced the number of peptide-specific T cells, allowing HLA/peptide multimer-guided T cell cloning. We succeeded in demonstrating that the established HLA-A2-restricted CTL clones recognized HLA-A2⁺ APCs exogenously loaded with the respective melanoma peptide as well as melanoma cells processing and presenting these peptides in the context of HLA-A2. We were not able to show that these melanoma-reactive CTL clones were stimulated by autologous dendritic cells pulsed with melanoma-derived hsp. These results are discussed with respect to various models for proving the role of hsp in T cell stimulation and to recent findings that part of the immunological antitumor activities reported for hsp are independent of the chaperoned peptides.

This article has been cited by other articles:

				R. Demine and P. Walden Testing the Role of gp96 as Peptide Chaperone in Antigen Processing J. Biol. Chem., May 6, 2005; 280(18): 17573 - 17578. [Abstract] [Full Text] [PDF]

				H. Li, M. Zhou, J. Han, X. Zhu, T. Dong, G. F. Gao, and P. Tien Generation of Murine CTL by a Hepatitis B Virus-Specific Peptide and Evaluation of the Adjuvant Effect of Heat Shock Protein Glycoprotein 96 and Its Terminal Fragments J. Immunol., January 1, 2005; 174(1): 195 - 204. [Abstract] [Full Text] [PDF]