T-cell receptor peptide therapy in EAE and MS.
Synthetic peptides corresponding to germline TCR V beta 8.2 sequences overexpressed by Lewis rat encephalitogenic T cells are effective in the prevention and treatment of autoimmune encephalomyelitis (EAE). In evaluating optimal conditions for identifying disease-relevant target V beta genes, we found that the biased expression of V beta 8.2 was most pronounced in the CNS among activated, IL-2 responsive T cells, but was weakly reflected in the cerebrospinal fluid. Evaluation of basic protein reactive T cells from patients with multiple sclerosis revealed biased expression of V beta 5.2 and to a lesser degree, V beta 6.1. Treatment of 11 MS patients with synthetic TCR V beta 5.2 and V beta 6.1 CDR2 peptides boosted the frequency of anti-TCR reactive T cells in a majority of patients, without compromising recall immunity or causing side effects. TCR peptides may be useful in the treatment of human autoimmune diseases, providing that disease-relevant V genes can be identified.
Vandenbark
A A
AA
V.A. Medical Center, Portland, OR 97201.
Bourdette
D N
DN
Whitham
R
R
Chou
Y K
YK
Hashim
G A
GA
Offner
H
H
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology / Q000628:therapy*; D004676:Myelin Basic Protein / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*
D004676:Myelin Basic Protein; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta