Model of stimulation-responsive splicing and strategies in identification of immunogenic isoforms of tumor antigens and autoantigens.

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.