T-CELL RECEPTOR (TCR) USAGE DETERMINES DISEASE SUSCEPTIBILITY IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS - STUDIES WITH TCR V-BETA-8.2 TRANSGENIC MICE

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease that can be induced in laboratory animals by immunization with the ma jor myelin proteins, myelin basic protein (MBP) and proteolipid protei n (PLP). We analyzed the role of the T cell receptor (TCR) repertoire in susceptibility to EAE induced by these two autoantigens. Autoreacti ve T cells induced after immunization with MBP use a limited set of TC R. In contrast, we demonstrate that T cell clones that recognize the e ncephalitogenic PLP epitope (PLP 139-151) use diverse TCR genes. When the TCR repertoire is limited by introduction of a novel rearranged TC R V beta 8.2 chain in transgenic SJL mice, EAE could be induced in the transgenic mice by immunization with the encephalitogenic epitopes of PLP, but not with the encephalitogenic epitope of MBP. Thus, skewing the TCR repertoire affects the susceptibility to EAE by immunization w ith MBP but not with PLP. These data demonstrate the biological conseq uences of the usage of a more diverse T cell repertoire in the develop ment of an autoimmune disease.