This proposal is based on the premise that idiotype (ld) and anti-ld networks are involved in the inflammatory demyelination of the central nervous system which occurs in multiple sclerosis and experimental allergic encephalomyelitis. It is hypothesized that there is a sharing of lds between the T cell receptor found on encephalitogenic T cells and antibody to the dame myelin basic protein (MBP) peptide. Through immunization with a complementary peptide, i.e., a peptide encoded by RNA complementary to the mRNA of the peptide or epitope of interest, an anti-ld with selective specificity can be produced. These anti-lds are capable of modulating humoral and cellular immune activities in vitro. The further characterization of the in vitro effects of these anti-lds and the analysis of their in vivo impact on immunopathological processes are the goals of this proposal.
The specific aims will be: (1) to define the mechanism through which monoclonal anti-ld inhibits the synthesis by murine hybridomas of ld-bearing monoclonal antibodies to MBP peptides. (2) to characterize the effect of anti-ld on T cell lines and clones expressing a T cell receptor whose clonotype recognizes the same MBP peptide as does the ld-bearing monoclonal antibody. (3) to determine the effect of anti-ld reacting with the ld against the encephalitogenic MBP peptide acetyl 1-9 on the development of experimental allergic encephalomyelitis in PL/J mice. (4) to determine the effect of immunization with a peptide complementary to MBP peptide acetyl 1-9 on the induction of experimental allergic encephalomyelitis in PL/J mice. (5) to determine if peripheral blood B cells, Epstein-Barr virus transformed B cells, serum or cerebrospinal fluid from normals, persons with multiple sclerosis or other neurological disease secrete or contain ld-bearing antibody reactive with selected human MBP peptides. The results of this investigation will furnish information relevant to the natural or therapeutically induced modulation of a systemic or in situ immune response in inflammatory demyelination as occurs in multiple sclerosis. With the knowledge of an encephalitogenic sequence of MBP or another molecule, the use of complementary peptides or anti-lds may permit the development of non-encephalitogenic, clinically feasible therapeutic agents.
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