T-cell receptor peptide therapy in EAE and MS.

A A Vandenbark; D N Bourdette; R Whitham; Y K Chou; G A Hashim; H Offner

PubMed · 7686833

T-cell receptor peptide therapy in EAE and MS.

A A Vandenbark·D N Bourdette·R Whitham·Y K Chou·G A Hashim·H Offner

Abstract

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.

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Animals Arthritis, Rheumatoid Encephalomyelitis, Autoimmune, Experimental Humans Immunotherapy Mice Multiple Sclerosis Myelin Basic Protein Peptides Rats Rats, Inbred Lew Receptors, Antigen, T-Cell, alpha-beta Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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A A Vandenbark, D N Bourdette, R Whitham, Y K Chou, G A Hashim, H Offner. T-cell receptor peptide therapy in EAE and MS.. https://pubmed.ncbi.nlm.nih.gov/7686833/

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