Epitope spreading occurs in active but not passive EAE induced by myelin basic protein

Area of Science:

• Neuroimmunology
• Autoimmune Diseases
• Central Nervous System (CNS) Inflammation

Background:

• Experimental allergic encephalomyelitis (EAE) models autoimmune demyelinating diseases like multiple sclerosis (MS).
• Epitope spreading, a change in T cell response specificity during disease, is key for MS therapeutic strategies.
• EAE's clinical and pathological outcomes vary with host factors and induction methods.

Purpose of the Study:

• To investigate epitope spreading in a passive EAE model in SJL/J mice, chosen for its clinical and neuropathological similarity to MS.
• To determine if T cell responses broaden to other myelin antigens during disease progression.
• To compare epitope spreading in passive versus active EAE models.

Main Methods:

• Induction of passive EAE using T cells specific for whole 18.5 kDa myelin basic protein (MBP).
• Monitoring T cell responsiveness to immunodominant (MBP 87-106) and subdominant (MBP 16-35) regions, and to proteolipid protein (PLP) 139-151.
• Comparison with active EAE induced by MBP.

Main Results:

• Progressive increase in T cell responsiveness to MBP 87-106 observed.
• No evidence of intermolecular spreading to PLP 139-151 or intramolecular spreading to MBP exon 2.
• No shift in immunodominance towards MBP 16-35.
• Epitope spreading to PLP 139-151 observed in active EAE, but not in passive EAE.

Conclusions:

• Passive EAE induced with whole MBP-specific T cells shows limited epitope spreading.
• Immune responses in passive and active EAE models differ significantly.
• Findings suggest minimal epitope spreading in chronic relapsing demyelinating disease initiated without exogenous antigen or adjuvants.