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 regula tory idiotope in Lewis rats developing experimental autoimmune encepha lomyelitis (EAE). The purpose of the present study was to determine if additional regulatory regions were contained within the V beta 8.2 se quence expressed by most encephalo-genic T cells, A comprehensive stra tegy utilizing V beta 8+ hybridomas, a recombinant (r) V beta 8.2 mole cule, and overlapping synthetic V alpha 8.2 peptides reconfirmed the n atural recognition of the 39-59 idiotope, and revealed a second immuno dominant 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 immunog enic, and each was recognized after immunization of Lewis rats with V beta 8+ cells or rV beta 8.2, indicating the preservation of these epi topes during the processing of the V beta 8.2 chain. Moreover, both ep itopes were recognized naturally by T cells from rats developing or re covering from EAE that had never been purposefully immunized,vith V be ta 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 r eports of CFA interference in EAE. (C) 1996 Wiley-Liss, Inc.