title: Optimal T-cell receptor affinity for inducing autoimmunity.
abstract: T-cell receptor affinity for self-antigen has an important role in establishing self-tolerance. Three transgenic mouse strains expressing antigens of variable affinity for the OVA transgenic-I T-cell receptor were generated to address how TCR affinity affects the efficiency of negative selection, the ability to prime an autoimmune response, and the elimination of the relevant target cell. Mice expressing antigens with an affinity just above the negative selection threshold exhibited the highest risk of developing experimental autoimmune diabetes. The data demonstrate that close to the affinity threshold for negative selection, sufficient numbers of self-reactive T cells escape deletion and create an increased risk for the development of autoimmunity.
authors.affiliation: Departments of Biomedicine and Nephrology, University Hospital Basel and University of Basel, CH-4031 Basel, Switzerland;
authors.forename: Sabrina
authors.initials: S
authors.lastname: Koehli
authors.affiliation: Departments of Biomedicine and Nephrology, University Hospital Basel and University of Basel, CH-4031 Basel, Switzerland;
authors.forename: Dieter
authors.initials: D
authors.lastname: Naeher
authors.affiliation: Departments of Biomedicine and Nephrology, University Hospital Basel and University of Basel, CH-4031 Basel, Switzerland;
authors.forename: Virginie
authors.initials: V
authors.lastname: Galati-Fournier
authors.affiliation: Swiss Vaccine Research Institute, CH-1066 Epalinges, Switzerland; and Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, 1011 Lausanne, Switzerland.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zehn
authors.affiliation: Departments of Biomedicine and Nephrology, University Hospital Basel and University of Basel, CH-4031 Basel, Switzerland; ed.palmer@unibas.ch.
authors.forename: Ed
authors.initials: E
authors.lastname: Palmer
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D001667:Binding, Competitive / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin
keywords: T cell; TCR; affinity; autoimmunity; tolerance