Common sequence on distinct V beta genes defines a protective idiotope in experimental encephalomyelitis

Synthetic TCR peptides expressed by encephalitogenic T cells can induce both cellular and humoral responses that protect against experimental encephalomyelitis. In the Lewis rat, encephalitogenic T cells predominantly express V beta 8.2, and a peptide in the CDR2 region representing residues 39-59 could both protect against and treat experimental autoimmune encephalitis (EAE). Similarly, the homologous and cross reactive 39-59 peptide from V beta 8.6 expressed by an EAE-protective clone also had protective and therapeutic activity against EAE. The consensus sequence between the V beta 8.2 and V beta 8.6 peptides, which included residues 44-54, was postulated to contain the protective idiotope. In this report, we demonstrate that this peptide, designated V beta 8-44-54, has comparable activity to the longer peptides for treating both active and passive EAE. Similar to the longer V beta 8.2-39-59 peptide, the V beta 8-44-54 peptide stimulates protective TCR peptide-specific CD4+, CD8dim T cells restricted by MHC I. We also report for the first time the recovery of V beta 8-44-54 reactive T cells that express a variety of V beta genes in their T-cell receptor (TCR), including V beta 4, 8, 10, 12, 15, 17, 19, and 20. Taken together, these data establish that the V beta 8-44-54 sequence constitutes an important autoregulatory idiotope in EAE.(ABSTRACT TRUNCATED AT 250 WORDS)