Tumour-specific MHC-class-II-restricted responses after in vitro sensitization to synthetic peptides corresponding to gp100 and Annexin II eluted from melanoma cells |
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Authors: | Kun Li Medi Adibzadeh Thomas Halder Hubert Kalbacher Susanne Heinzel Claudia Müller Jesper Zeuthen Graham Pawelec |
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Institution: | (1) Tübingen Ageing and Tumour Immunology Group, University of Tübingen Center for Medical Research, Derendingen, Tübingen, Germany, DE;(2) Section for Transplantation Immunology and Immunohaematology, Second Department of Internal Medicine, University of Tübingen Medical School, Tübingen, Germany, DE;(3) Medical and Natural Sciences Research Center, University of Tübingen, Tübingen, Germany, DE;(4) Danish Cancer Society, Copenhagen, Denmark, DK;(5) Medizinische Klinik, Otfried Müller-Strasse 10, D-72076 Tübingen, Germany e-mail: graham.pawelec@med.uni-tuebingen.de Tel.: +49-7071-298-2805; Fax: +49-7071-294464, DE |
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Abstract: | In a search for potentially tumour-specific MHC-class-II-restricted antigens, the immunogenicity of endogenous peptides that
had been eluted from HLA-DR molecules of the human melanoma cell line FM3 (HLA-DRB1*02x, DRB1*0401) was tested in vitro. Two
16-mers representing gp100 positions 44–59, and annexin II positions 208–223 bound well to isolated DRB1*0401 molecules and
are discussed here. HLA-DR-matched normal donors' T cells were cultured with peptide-pulsed artificial antigen-presenting
cells (CHO cells cotransfected with genes for HLA-DRB1*0401 and CD80 and coexpressing high levels of both human molecules).
Specific sensitization was achieved against both peptides, as measured in assays of autocrine proliferation and interleukin-2
secretion. Moreover, responses to native autologous melanoma cells but not to autologous B cells were also observed. In view
of the expression of fas by the activated T cells and of fas ligand by the melanoma cells, blockade of potential fas/fas-ligand
interactions was undertaken using monoclonal antibodies (mAb). The antagonistic fas-specific mAb M3, but not the fas agonist
M33, caused a markedly enhanced T cell response to FM3 cells. These results demonstrate that synthetic peptide antigens are
able to sensitize T cells in vitro for effective MHC-class-II-restricted recognition of melanoma cells.
Received: 12 April 1998 / Accepted: 23 April 1998 |
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Keywords: | HLA-DR-restricted tumour antigens Synthetic peptide antigens Tumour escape from immune responses Apoptosis Melanoma |
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