T. Yamamura et al., AN ALPHA-CHAIN TCR CDR3 PEPTIDE CAN ENHANCE EAE INDUCED BY MYELIN BASIC-PROTEIN OR PROTEOLIPID PROTEIN, Journal of neuroscience research, 45(6), 1996, pp. 706-713
Regulation of experimental autoimmune encephalomyelitis (EAE) can be i
nduced by anti-idiotype immunity against T cell receptor (TCR) fragmen
ts associated with major histocompatibility complex (MHC) molecules, H
owever, we have recently found that preimmunization with an alpha-chai
n TCR CDR3 peptide (LYFCAARSNYQL) derived from myelin basic protein (M
BP)-specific clones did not suppress but rather augmented the severity
of EAE induced by MBP-specific T cells in SJL/J mice. To test whether
CDR3 vaccination could control only a highly restricted T cell popula
tion, we studied the effect of the peptide against EAE induced by T ce
lls specific for different Ag/MHC ligands and autoimmune diseases affe
cting non-neural tissues, In contrast to expectations, the peptide was
found to augment not only EAE induced by MBP-specific T cells, but al
so proteolipid protein (PLP)-specific T cell- or PLP peptide-induced E
AE in SJL/J mice, and MBP-induced EAE and adjuvant arthritis (AA) in r
ats. The CDR3 peptide was neither inhibitory nor supportive for Ag-ind
uced activation of an encephalitogenic clone in vitro. In addition, th
e peptide treatment neither inhibited the induction of Ag-specific T c
ells nor altered the APC function of spleen cells. These findings, on
the one hand, confirm previous results showing TCR peptide-induced enh
ancement of the disease and, on the other hand, indicate that the TCR
CDR3 peptide may control T cells with broader Ag/MHC specificities tha
n could be expected, Structural similarity among TCR idiotypes of auto
immune T cells may partly account for these results. (C) 1996 Wiley-Li
ss, Inc.