title: Cloning genes encoding MHC class II-restricted antigens: mutated CDC27 as a tumor antigen.
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.
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10/2B42, 9000 Rockville Pike, Bethesda, MD 20892, USA. rongfu@pop.nci.nih.gov
authors.forename: R F
authors.initials: RF
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: A C
authors.initials: AC
authors.lastname: Atwood
authors.forename: S L
authors.initials: SL
authors.lastname: Topalian
authors.forename: S A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: 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
chemical_list: 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