T cell receptor peptide therapy for autoimmune disease.
Synthetic peptides corresponding to germline T cell receptor (TCR) V beta sequences shared by encephalitogenic T cells can prevent and treat experimental autoimmune encephalomyelitis in rats. The operative mechanism apparently involves boosting of anti-TCR immunity that develops during the course of experimental autoimmune encephalomyelitis (EAE), leading to the induction of autoregulatory T cells and antibodies. Striking parallels are present between patients with multiple sclerosis and animals with EAE in the T cell frequency and TCR V gene bias of BP reactive T cells, suggesting the involvement of an encephalitogenic process in multiple sclerosis. Preliminary trials with the appropriate human TCR peptides indicate that anti-TCR immunity can be boosted efficiently and safely, with concomitant loss of BP response, thus providing an effective strategy for selective regulation of autoimmunity in man.
Vandenbark
A A
AA
Neuroimmunology Research, Veterans Affairs Medical Center, Portland, OR 97201.
Chou
Y K
YK
Bourdette
D N
DN
Whitham
R
R
Hashim
G A
GA
Offner
H
H
D000818:Animals; D000917:Antibody Formation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C066890:T cell receptor-V(beta)8-39-59 peptide