CHARACTERISTICS OF THE T-LYMPHOCYTES INVOLVED IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

Both heterogeneity and restricted heterogeneity of the encephalitogeni c myelin basic protein (MBP) peptide-specific T cell receptors (TCRs) were demonstrated in inbred animals depending on the strain-specific g enetic characteristics, the stage of the disease, the compartment of t he lymphocytes obtained and the methodology used. Nevertheless, the si milar features of some MBP-specific TCRs demonstrated across species s uggest that conservation of these autoantigen-specific molecules undou btedly exists, even though the degree of this conservation is controve rsial, However, the unequivocal heterogeneity of the immune response d irected at one of the most important myelin constituents, proteolipid lipoprotein (PLP), which occurs either as a primary or a secondary eve nt during experimental allergic encephalomyelitis (EAE), indicates the complexity of the in vivo situation. Intramolecular and intermolecula r spreading of antigen specificity during the course of the disease in dicates that a TCR directed therapy may not be the choice of intervent ion in established disease even in individual strains of laboratory an imals with restricted heterogeneity of the primary MBP-specific respon se. Studying the sequence of events, the recruited regulatory cells an d cytokines, and the stromal factors controlling persistence or death of activated, memory cells in the tissue lesion, may reveal new therap eutic modalities with more universal applicabilities.