A CROSS-REACTIVE IDIOTOPE ON T-CELLS FROM PL J MICE AND LEWIS RATS THAT RECOGNIZES DIFFERENT MYELIN BASIC-PROTEIN ENCEPHALITOGENIC EPITOPESBUT IS RESTRICTED BY TCR V-BETA-8.2/

Encephalitogenic T cells of both PL/J mice and Lewis rats are restrict ed by TCR V beta 8.2, although they recognize different epitopes in th e myelin basic protein (MBP) molecule. We sought the presence of a cro ss-reactive idiotope (Id) in encephalitogenic T cells of Lewis rats by examining the effects of mAb F30 anti-Id, which recognized a TCR Id i n PL/J T cells, on the encephalitogenic LR88L1 cell line derived from Lewis rats and specific for guinea pig MBP peptide 68-88. The LR88L1 c ells were I-A restricted and TCR V beta 8.2(+), and their proliferatio n and secretion of IL-2 and TNF-alpha induced by guinea pig MBP peptid e 68-88 was inhibited by mAb F30 anti-id. As shown by FACS analysis an d by immunoprecipitation of TCR from radiolabeled LR88L1 cell lysates, the F30 anti-Id bound to the TCRs of V beta 8.2(+) LR88L1 cells. In a ddition, TCR sequences in the F30(+) population of LR88L1 cells were t he same as those of encephalitogenic Lewis rat T cells published previ ously. The F30(+) LR88L1 cells showed reduced encephalitogenicity comp ared with F30(-) or unsorted LR88L1 cells. The mechanism for this redu ction by anti-Id probably resulted from the induction of anergy, in th at IL-2 reversed the anti-Id effect. The control LR99L1 T cell line, a lso encephalitogenic, but specific for MBP peptide 87-99 and I-E, and not TCR V beta 8.2 restricted, failed to react with, or have its cytok ine secretion inhibited by, mAb F30 anti-id. These results demonstrate an interspecies cross-reactive Id expressed in common by encephalitog enic T cells that share a similar TCR, although they differ in MBP epi tope specificity. These findings suggest that a common Id restricted b y TCR, but less restricted by the encephalitogenic epitope, and recogn ized by the Id-bearing autoreactive T cells may represent an immunothe rapeutic approach for treating autoimmune demyelinating diseases.