Abstract
Soluble MHC-peptide complexes, commonly referred to as tetramers, have been shown to induce strong cross-linking of TCR and CD8, resulting in a vigorous activation followed by a rapid non-apoptotic CD8(+) T cell death. This has limited tetramer use for antigen-specific T cells isolation and cloning, as sorted tetramer positive cells were shown to possess compromised functional integrity. Here we show that the cross-linking of a secondary co-stimulatory signal into oligomeric MHC:peptide complexes prevents such cell death, and in contrast strongly stimulates antigen-specific T cell responses. Such soluble antigen-presenting complexes (sAPCs) containing MHC:peptide complexes linked to either anti-CD27 or anti-CD28 antibodies were capable of priming and expanding HLA-A*0201 restricted CMV specific T cells and also of generating functional HLA-A*0301 restricted BCR/ABL-specific T cell responses. These sAPCs constitute an encouraging alternative method for generating antigen-specific T cells that could be applied to a variety of antigens.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / metabolism*
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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CD28 Antigens / immunology
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CD28 Antigens / metabolism
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Cell Proliferation
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Flow Cytometry
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Fusion Proteins, bcr-abl / immunology
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Fusion Proteins, bcr-abl / metabolism
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HLA-A Antigens / immunology*
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HLA-A2 Antigen
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HLA-A3 Antigen
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology
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Major Histocompatibility Complex / immunology
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Monocytes / cytology
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Monocytes / immunology
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Monocytes / metabolism
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Peptide Fragments / immunology*
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Streptavidin / metabolism*
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T-Lymphocytes / immunology*
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
Substances
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Antibodies, Monoclonal
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CD28 Antigens
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HLA-A Antigens
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HLA-A*02:01 antigen
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HLA-A*03:01 antigen
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HLA-A2 Antigen
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HLA-A3 Antigen
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Peptide Fragments
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Tumor Necrosis Factor Receptor Superfamily, Member 7
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Streptavidin
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Fusion Proteins, bcr-abl