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.