Cloning genes encoding MHC class II-restricted antigens: mutated CDC27 as a tumor antigen.
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.
Wang
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RF
Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10/2B42, 9000 Rockville Pike, Bethesda, MD 20892, USA. rongfu@pop.nci.nih.gov
Wang
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X
Atwood
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Topalian
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Rosenberg
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SA
D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000276:immunology*; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D000939:Epitopes / Q000276:immunology; D015798:HLA-DR1 Antigen / Q000276:immunology; D015804:HLA-DR4 Antigen / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology; D017354:Point Mutation; D011993:Recombinant Fusion Proteins; D014162:Transfection; D014305:Triose-Phosphate Isomerase / Q000235:genetics / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; C577366:CDC27 protein, human; D018797:Cell Cycle Proteins; D000939:Epitopes; D015798:HLA-DR1 Antigen; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II; D011993:Recombinant Fusion Proteins; C045084:invariant chain; D014305:Triose-Phosphate Isomerase