The effects of citrullination or variable amino-terminus acylation on the encephalitogenicity of human myelin basic protein in the PL/J mouse

Abstract

The post-translational modifications of myelin basic protein (MBP) in the form of citrullination and varying length of amino-terminus acylation may modify the biological functions and immunological features of MBP. Both modifications influence the reaction of antibodies and specific T cells recognizing MBP. The present study was undertaken to compare the encephalitogenicity of the citrullinated isomer of MBP (MBP-C8) with the unmodified isomer of MBP (MBP-C1) and to determine if the length of amino-terminal acylation of MBP peptide 1–21 altered an encephalitogenic epitope. MBP-C8, whether from patients with or without multiple sclerosis (MS), and MBP-C1 could induce active experimental allergic encephalomyelitis (EAE) in PL/J mice. A trend of reduced severity of EAE was observed in MBP-C8-injected animals. An increase in the length of amino-terminus fatty acid decreased the encephalitogenicity of MBP peptide 1–21 for both active and adoptive EAE in PL/J mice. Only lymph node cells sensitive to MBP peptide acetyl 1–21 and butyl 1–21 could transfer clinical EAE. In adoptive EAE, MBP peptides hexyl and octyl 1–21 induced moderate histopathological but no clinical change, whereas MBP peptide decyl 1–21 caused neither. A broadening in the antibody response could be detected in the sera of mice with active EAE induced by MBP-acylated peptides 1–21. Our findings demonstrate that encephalitogenicity is retained in the presence of citrullination but that the length of amino-terminus acylation diminishes the encephalitogenicity of MBP in the PL/J mouse. These findings may be relevant to MS where central nervous system myelin shows differences from normal in both MBP-C8 content and MBP amino-terminus acylation.