Natural immunodominant and experimental autoimmune encephalomyelitis-protective determinants within the Lewis rat V beta 8.2 sequence include CDR2 and framework 3 idiotopes.

The V beta 8.2-39-59 peptide has served as a prototypic natural regulatory idiotope in Lewis rats developing experimental autoimmune encephalomyelitis (EAE). The purpose of the present study was to determine if additional regulatory regions were contained within the V beta 8.2 sequence expressed by most encephalogenic T cells. A comprehensive strategy utilizing V beta 8+ hybridomas, a recombinant (r) V beta 8.2 molecule, and overlapping synthetic V beta 8.2 peptides reconfirmed the natural recognition of the 39-59 idiotope, and revealed a second immunodominant and EAE-protective determinant residing within residues 71-90. Both the V beta 8.2-39-59 and V beta 8.2-71-90 peptides were immunogenic, and each was recognized after immunization of Lewis rats with V beta 8+ cells or rV beta 8.2, indicating the preservation of these epitopes during the processing of the V beta 8.2 chain. Moreover, both epitopes were recognized naturally by T cells from rats developing or recovering from EAE that had never been purposefully immunized with V beta 8.2 peptides or rV beta 8.2. Of additional interest, the V beta 8.2-31-50 peptide was recognized by T cells from some rats immunized with complete Freund's adjuvant (CFA) alone. This peptide possessed mildly protective activity against EAE and thus could account for sporadic reports of CFA interference in EAE.