Induction of experimental autoimmune arthritis by a public epitope of the T cell receptor variable alpha domain of an arthritogenic T cell clone.
T cell receptor (TCR) peptide immunizations have been demonstrated to protect against experimental autoimmune diseases. These findings have led to clinical trials employing TCR peptides in multiple sclerosis and rheumatoid arthritis patients. Previously, we identified a strongly immunogenic region of the TCR alpha chain of an arthritogenic T cell clone (AV11 66-80). In this report, we show that rats immunized with AV11 66-80 developed arthritis with clinical symptoms and histology similar to adjuvant arthritis (AA). Transfer of this disease into naive rats using AV11 66-80-specific T cells proved the T cell-mediated character of the disease. The AV11 66-80 arthritic rats developed resistance to Mycobacterium tuberculosis-induced AA, indicating that both forms of arthritis depended on similar regulatory mechanisms. This first demonstration of TCR peptide-induced arthritis, together with an earlier report on a polymorphism in this very same AV11 66-80 region involved in arthritis resistance in mice, suggests a central role of the public epitope AV11 66-80 in the control of autoimmune arthritis. Although TCR peptide immunizations can be exploited to prevent experimental autoimmunity, caution should be taken in the induction of TCR peptide-specific T cells for immunotherapy to avoid adverse effects as shown here.
van Tienhoven
E A
EA
Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
van Kooten
P J
PJ
Veenstra
J G
JG
van der Hage
M H
MH
van Eden
W
W
Broeren
C P
CP
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology*; D000939:Epitopes; D007114:Immunization; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta