Protection against experimental encephalomyelitis: Idiotypic autoregulation induced by a nonencephalitogenic T cell clone expressing a cross-reactive T cell receptor V gene

The recovery process in experimental autoimmune encephalomyelitis (EAE) in Lewis rats is characterized by an increasing diversity of T cell clones directed at secondary epitopes of myelin basic protein. Of particular interest, residues 55 to 69 of guinea pig basic protein could induce protection against EAE. A nonencephalitogenic T cell clone, C4_55-69, that was specific for this epitope transferred protection against both active and passive EAE. Clone C4_55-69 was found to express Vβ8.6 in its Ag receptor, and residues 39 to 59 of the TCR Vβ8.6 sequence were found to be highly crossreactive with the corresponding residues 39 to 59 of TCR Vβ8.2, which is known to induce protective anti-idiotypic T cells and antibodies. Like the TCR Vβ8.2_39-59 peptide, the Vβ8.6_39-59 sequence induced autoregulation and provided effective treatment of established EAE. Thus, the EAE-protective effect of the guinea pig basic protein 55-69 sequence was most likely mediated by T cell clones such as C4_55-69 that could efficiently induce anti-TCR immunity directed at a cross-reactive regulatory idiotope.