T-cell avidity and tuning: the flexible connection between tolerance and autoimmunity.
Thymic T-cell selection mechanisms generate a cross-reactive, self-MHC restricted peripheral T-cell pool. Affinity and avidity are of profound influence on this selection and the generation of immunity. Autoreactive T cells can escape thymic deletion by lowering their avidity and retain this "tuned" state in the periphery. Upon activation, tuned T cells can cause autoimmunity, while immunotherapeutic strategies may be hampered by existing T-cell tolerance. The regulation of T-cell avidity and tuning therefore determines the balance between tolerance and autoimmunity and should be taken into account in the design of therapeutic strategies aimed at T-cell reactivity.
van den Boorn
Jasper G
JG
Netherlands Institute for Pigment Disorders and Department of Dermatology, AMC, University of Amsterdam, Amsterdam, The Netherlands. j.g.vandenboorn@amc.uva.nl
Le Poole
I Caroline
IC
Luiten
Rosalie M
RM
D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007167:Immunotherapy; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell