Tolerance induction by acylated peptides: effect on encephalitogenic T cell lines.
We reported previously that acylation of an encephalitogenic peptide of myelin basic protein (MBP68-86) by attachment of palmitoyl chloride (PAL68-86) converted this peptide into a powerful tolerogen for EAE in the Lewis rat. In this study we show that T cell lines derived from a PAL68-86-protected rat proliferated poorly to MBP68-86 in vitro, even after repeated passages in this peptide and IL-2. Conversely, T cell lines derived from untreated rats that were challenged with MBP68-86 or PAL68-86 in CFA responded vigorously to MBP68-86 when propagated for many passages in this peptide but became gradually unresponsive after being propagated in the presence of PAL68-86. The modulation of the T cell lines by PAL68-86 in vitro was reflected by a significant reduction in their ability to transfer EAE to recipients. A high percentage of cells stained with an anti-Vbeta8.2 antibody, regardless of whether they were propagated in the presence of unmodified or acylated peptide. The results are consistent with the notion that tolerance induced by PAL68-86 operates by functional inactivation and provide the basis for the use of acylated peptides in the antigen-specific treatment of autoimmune diseases.
St Louis
J
J
The John P. Robarts Research Institute, University of Western Ontario, Health Sciences Center, London, Ontario, N6A 5C1, Canada.
Zhang
X M
XM
Heber-Katz
E
E
Uniyal
S
S
Robbinson
D
D
Singh
B
B
Strejan
G H
GH
D000215:Acylation; D000818:Animals; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D007108:Immune Tolerance; D008297:Male; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology*; D019308:Palmitic Acid / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
D004676:Myelin Basic Protein; D010446:Peptide Fragments; C110235:myelin basic protein 68-86; D019308:Palmitic Acid