title: Model of stimulation-responsive splicing and strategies in identification of immunogenic isoforms of tumor antigens and autoantigens.
abstract: We recently proposed a novel model of stimulation-responsive splicing for the selection of autoantigens and self-tumor antigens. Our model theorizes that the significantly higher rates of alternative splicing of autoantigen and self-tumor antigen transcripts that occur in response to stimuli could induce extra-thymic expression of untolerized antigen epitopes for elicitation of autoimmune and anti-tumor responses. To facilitate the identification of immunogenic isoforms of antigens, we have developed strategies using improved SEREX in conjunction with database-mining and immunogenic isoform mapping. Identification of immunogenic isoforms of autoantigens and self-tumor antigens is very important for the development of novel therapeutics and diagnostic tools for autoimmune diseases and tumors, such as: (1) autoantigen isoform microarrays for disease diagnosis and prognosis; (2) autoantigen isoform-specific tolerizing vaccines and splicing-redirection therapies, as well as (3) immunogenic antigen isoform-specific immunotherapy for tumors.
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, 3420 North Broad Street, Medical Research Building, Suite 300, Philadelphia, PA 19140, USA. xfyang@temple.edu
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Irene H
authors.initials: IH
authors.lastname: Chen
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Xiong
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yang
mesh_terms: D017398:Alternative Splicing; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology*; D030541:Databases, Genetic; D015536:Down-Regulation; D000939:Epitopes / Q000378:metabolism; D042822:Genomic Instability; D006801:Humans; D008957:Models, Genetic; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology*; D020033:Protein Isoforms / Q000276:immunology*; D020543:Proteome / Q000235:genetics; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D001324:Autoantigens; D000939:Epitopes; D020033:Protein Isoforms; D020543:Proteome