Abstract
It is established that mutations in viral antigenic epitopes, or antigenic drifts, allow viruses to escape recognition by both Ab's and T lymphocytes. It is unclear, however, whether tumor cells can escape immune recognition via antigenic drift. Here we show that adoptive therapy with both monoclonal and polyclonal transgenic CTLs, specific for a natural tumor antigen, P1A, selects for multiple mutations in the P1A antigenic epitope. These mutations severely diminish T cell recognition of the tumor antigen by a variety of mechanisms, including modulation of MHC:peptide interaction and TCR binding to MHC:peptide complex. These results provide the first evidence for tumor evasion of T cell recognition by antigenic drift, and thus have important implications for the strategy of tumor immunotherapy.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, Neoplasm / genetics*
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Antigens, Neoplasm / immunology*
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Clone Cells / immunology
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Clone Cells / pathology
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DNA Mutational Analysis
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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Disease Models, Animal
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Epitopes / genetics
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Epitopes / immunology
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Genetic Drift*
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Immunotherapy, Adoptive / adverse effects
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Major Histocompatibility Complex / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Neoplasm Transplantation
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Plasmacytoma / immunology*
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Plasmacytoma / pathology
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Plasmacytoma / therapy
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / transplantation
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Tumor Escape / genetics
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Tumor Escape / immunology*
Substances
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Antigens, Neoplasm
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DNA-Binding Proteins
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Epitopes
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Rag2 protein, mouse
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Receptors, Antigen, T-Cell, alpha-beta
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V(D)J recombination activating protein 2
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tumor rejection antigen P815A, mouse