An alpha-chain TCR CDR3 peptide can enhance EAE induced by myelin basic protein or proteolipid protein.
Regulation of experimental autoimmune encephalomyelitis (EAE) can be induced by anti-idiotype immunity against T cell receptor (TCR) fragments associated with major histocompatibility complex (MHC) molecules. However, we have recently found that preimmunization with an alpha-chain TCR CDR3 peptide (LYFCAARSNYQL) derived from myelin basic protein (MBP)-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 population, we studied the effect of the peptide against EAE induced by T cells specific for different Ag/MHC ligands and autoimmune diseases affecting non-neural tissues. In contrast to expectations, the peptide was found to augment not only EAE induced by MBP-specific T cells, but also proteolipid protein (PLP)-specific T cell- or PLP peptide-induced EAE in SJL/J mice, and MBP-induced EAE and adjuvant arthritis (AA) in rats. The CDR3 peptide was neither inhibitory nor supportive for Ag-induced activation of an encephalitogenic clone in vitro. In addition, the peptide treatment neither inhibited the induction of Ag-specific T cells nor altered the APC function of spleen cells. These findings, on the one hand, confirm previous results showing TCR peptide-induced enhancement of the disease and, on the other hand, indicate that the TCR CDR3 peptide may control T cells with broader Ag/MHC specificities than could be expected. Structural similarity among TCR idiotypes of autoimmune T cells may partly account for these results.
Yamamura
T
T
Department of Demyelinating Disease and Aging, National Institute of Neuroscience, Tokyo, Japan.
Geng
T C
TC
Kozovska
M F
MF
Yokoyama
K
K
Cohen
I R
IR
Tabira
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental; D003921:Diabetes Mellitus, Experimental; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology*; D000939:Epitopes; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D051381:Rats; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D014611:Vaccination
D000939:Epitopes; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D017260:Receptor-CD3 Complex, Antigen, T-Cell