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

AbstractSynthetic 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 Vβ8.2, 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 Vβ8.6 expressed by an EAE‐protective clone also had protective and therapeutic activity against EAE. The consensus sequence between the Vβ8.2 and Vβ8.6 peptides, which included residues 44–54, was postulated to contain the protective idiotope. In this report, we demonstrate that this peptide, designated Vβ8‐44–54, has comparable activity to the longer peptides for treating both active and passive EAE. Similar to the longer Vβ8.2‐39–59 peptide, the Vβ8‐44–54 peptide stimulates protective TCR peptide‐specific CD4 +, CD8dim T cells restricted by MHC I. We also report for the first time the recovery of Vβ8‐44–54 reactive T cells that express a variety of Vβ genes in their T‐cell receptor (TCR), including Vβ4, 8, 10, 12, 15, 17, 19, and 20. Taken together, these data establish that the Vβ8‐44–54 sequence constitutes an important autoregulatory idiotope in EAE. Moreover, the heterogeneity observed in the TCR expressed by anti‐Vβ8‐44–54 T cells suggests that the mechanism that produces biased V gene use in response to myelin basic protein (BP) is distinct from that which shapes the V gene repertoire of the regulatory T cells.