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The effects of citrullination or variable amino-terminus acylation on the encephalitogenicity of human myelin basic
S R Zhou1, M A Moscarello, J N Whitaker
1Department of Neurology, University of Alabama at Birmingham 35294, USA.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Citrullination of myelin basic protein (MBP) retains its encephalitogenicity, while longer amino-terminal acylation reduces it. These modifications impact immune responses in experimental allergic encephalomyelitis (EAE) models.
Area of Science:
- Neuroimmunology
- Protein Chemistry
Background:
- Post-translational modifications (PTMs) of myelin basic protein (MBP), including citrullination and N-terminal acylation, can alter its immunological functions.
- These modifications influence the recognition of MBP by antibodies and T cells, potentially affecting autoimmune responses.
Purpose of the Study:
- To compare the encephalitogenic potential of citrullinated MBP (MBP-C8) versus unmodified MBP (MBP-C1).
- To investigate how the length of N-terminal acylation on an MBP peptide (1-21) affects its encephalitogenicity.
Main Methods:
- Induction of active and adoptive experimental allergic encephalomyelitis (EAE) in PL/J mice using modified MBP and MBP peptides.
- Assessment of clinical EAE severity and histopathological changes.
- Analysis of antibody responses in sera of EAE-induced mice.
Main Results:
- Both MBP-C8 and MBP-C1 induced EAE, with a trend towards reduced severity in MBP-C8-treated mice.
- Increasing the length of N-terminal fatty acid acylation on MBP peptide 1-21 decreased its encephalitogenicity.
- Lymph node cells sensitized to acetylated and butylated MBP peptide 1-21 were capable of transferring EAE.
Conclusions:
- Encephalitogenicity of MBP is maintained despite citrullination.
- The length of N-terminal acylation significantly diminishes the encephalitogenic capacity of MBP peptides.
- These findings highlight the role of MBP PTMs in modulating autoimmune responses relevant to demyelinating diseases.