title: Immunological perspective of self versus tumor antigens: insights from the RIP-gp model.
abstract: Self-reactive T cells in the body are controlled by mechanisms of peripheral tolerance that limit their activation and induction of immune pathology. Our understanding of these mechanisms has been advanced by the use of tissue-specific promoters to express neo-self-antigens. Here, we present findings using the RIP-gp (rat insulin promoter-glycoprotein) transgenic mouse, which expresses the lymphocytic choriomeningitis virus glycoprotein (LCMV-gp) specifically in the pancreatic β islet cells. T cells responsive to this antigen remain ignorant of the LCMV-gp expressed by the islets, and breaking tolerance is dependent upon the maturation status of antigen-presenting cells, the avidity of the T-cell receptor ligation, and the level of major histocompatibility complex expression in the pancreas. Furthermore, decreased activity of Casitas B-lineage lymphoma b, a negative regulator of T-cell receptor signaling, can allow recognition and destruction of the pancreatic islets. This review discusses the roles of these factors in the context of anti-tissue responses, both in the setting of autoimmunity and in anti-tumor immunity.
authors.affiliation: Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, ON, Canada.
authors.forename: Dilan
authors.initials: D
authors.lastname: Dissanayake
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Gronski
authors.forename: Albert
authors.initials: A
authors.lastname: Lin
authors.forename: Alisha R
authors.initials: AR
authors.lastname: Elford
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D017634:Self Tolerance; D019076:Transgenes / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D001324:Autoantigens; D006023:Glycoproteins; D007328:Insulin; D014759:Viral Envelope Proteins; C479900:glycoprotein C, lymphocytic choriomeningitis virus