Abstract
In an effort to identify tumor-specific antigens recognized by CD4(+) T cells, an approach was developed that allows the screening of an invariant chain-complementary DNA fusion library in a genetically engineered cell line expressing the essential components of the major histocompatibility complex (MHC) class II processing and presentation pathway. This led to the identification of a mutated form of human CDC27, which gave rise to an HLA-DR4-restricted melanoma antigen. A mutated form of triosephosphate isomerase, isolated by a biochemical method, was also identified as an HLA-DR1-restricted antigen. Thus, this approach may be generally applicable to the identification of antigens recognized by CD4(+) T cells, which could aid the development of strategies for the treatment of patients with cancer, autoimmune diseases, or infectious diseases.
MeSH terms
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Antigen Presentation
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Antigens, Differentiation, B-Lymphocyte / genetics
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Antigens, Differentiation, B-Lymphocyte / immunology
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Antigens, Neoplasm / immunology*
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Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome
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CD4-Positive T-Lymphocytes / immunology
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Cell Cycle Proteins / genetics*
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Cell Cycle Proteins / immunology*
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Cell Line, Transformed
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Cloning, Molecular*
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Epitopes / immunology
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HLA-DR1 Antigen / immunology
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HLA-DR4 Antigen / immunology
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / immunology*
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Humans
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Lymphocytes, Tumor-Infiltrating / immunology*
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Melanoma / immunology
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Point Mutation
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Recombinant Fusion Proteins
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Transfection
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Triose-Phosphate Isomerase / genetics
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Triose-Phosphate Isomerase / immunology
Substances
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Antigens, Differentiation, B-Lymphocyte
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Antigens, Neoplasm
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Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome
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CDC27 protein, human
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Cell Cycle Proteins
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Epitopes
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HLA-DR1 Antigen
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HLA-DR4 Antigen
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Histocompatibility Antigens Class II
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Recombinant Fusion Proteins
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invariant chain
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Triose-Phosphate Isomerase