Natural immunodominant and experimental autoimmune encephalomyelitis-protective determinants within the lewis rat vβ8.2 sequence include CDR2 and framework 3 idiotopes

The Vβ8.2-39-59 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 Vβ8.2 sequence expressed by most encephalogenic T cells. A comprehensive strategy utilizing Vβ8+ hyhridomas, a recombinant (r) Vβ8.2 molecule, and overlapping synthetic Vβ8.2 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 Vβ8.2-39-59 and Vβ8.2-71-90 peptides were immunogenic, and each was recognized after immunization of Lewis rats with Vβ8 + cells or rVβ8.2, indicating the preservation of these epitopes during the processing of the Vβ8.2 chain. Moreover, both epitopes were recognized naturally by T cells from rats developing or recovering from EAE that had never been purposefully immunized with Vβ8.2 peptides or rVβ8.2. Of additional interest, the Vβ8.2-31-50 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.