Investigating the contribution of molecular mimicry with microbial peptides in the induction of neuroinflammation 2987
Year: 2025
Type: article
Abstract: Description Multiple sclerosis (MS) is an incurable autoimmune condition that affects more than 400,000 individuals in the United States. Characterized by the demyelination of neurons in the central nervous system (CNS), symptoms of MS include cognitive deficits, ataxia, and severe pain. Several environmental and genetic risk factors such as Epstein-Bar Virus infection and the DRB1*1501 haplotype have been identified, but the exact etiology of this disease remains unclear. It is generally accepted that autoreactive CD4+ T cells are the primary drivers of MS pathology, and previous reports showed that select microbial peptides are capable of stimulating myelin-specific T cell receptors (TCRs) via molecular mimicry. Therefore, we hypothesize that sub-pathogenic populations of myelin-specific T cells could be activated by molecular mimicry with microbial peptides and may be able to induce disease in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Using the EAE model and ELISPOT cytokine assays, our preliminary results indicate robust T cell tolerance towards myelin basic protein (MBP) peptides in DR2b transgenic mice. Further, while several HLA-DR2b reactive peptides induced T cell responses following immunization, they were unable to induce cross-reactive MBP-specific T cell responses. Together, the findings suggest that a preexisting pathogenic T cell repertoire may be required to induce neuroinflammation via molecular mimicry, which we are currently investigating. Funding Sources This work was supported by grant NIH grant R01NS117742 (T.G.F.), support by the Jesse H. & Mary Jones Gibbs Endowed Chair (T.G.F.), support by grant G12MD007591 from the National Institute on Minority Health and Health Disparities, and MARC (Maximizing Access to Research Careers) NIH/NIGMS Award: T34GM145507 (LS). Topic Categories Basic Autoimmunity (BA)
Source: The Journal of Immunology
Institution: The University of Texas at San Antonio
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416451279
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