Abstract
T cell responsiveness to an epitope is affected both by its affinity for the presenting MHC molecule and the affinity of the MHC-peptide complex for TCR. One limitation of cancer immunotherapy is that natural tumor antigens elicit relatively weak T cell responses, in part because high-affinity T cells are rendered tolerant to these antigens. We report here that amino acid substitutions in a natural MHC class I-restricted tumor antigen that increase the stability of the MHC-peptide-TCR complex are significantly more potent as tumor vaccines. The improved immunity results from enhanced in vivo expansion of T cells specific for the natural tumor epitope. These results indicate peptides that stabilize the MHC-peptide-TCR complex may provide superior antitumor immunity through enhanced stimulation of specific T cells.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alanine / metabolism
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Amino Acid Substitution
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Animals
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Antigens, Neoplasm / immunology*
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Antigens, Neoplasm / metabolism
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Clone Cells
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Colorectal Neoplasms / immunology*
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Cytotoxicity, Immunologic / immunology
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Epitopes, T-Lymphocyte / immunology*
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Epitopes, T-Lymphocyte / metabolism
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Female
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H-2 Antigens / metabolism*
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Histocompatibility Antigen H-2D
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Ligands
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Mice
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Mice, Inbred BALB C
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Oligopeptides / chemical synthesis
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Oligopeptides / immunology*
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Oligopeptides / metabolism*
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Receptor-CD3 Complex, Antigen, T-Cell / metabolism*
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Surface Plasmon Resonance
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T-Lymphocyte Subsets / immunology
Substances
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Antigens, Neoplasm
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Epitopes, T-Lymphocyte
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H-2 Antigens
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Histocompatibility Antigen H-2D
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Ligands
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Oligopeptides
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Receptor-CD3 Complex, Antigen, T-Cell
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Alanine