ArticlePloS one2010
Immunoproteasome LMP2 60HH variant alters MBP epitope generation and reduces the risk to develop multiple sclerosis in Italian female population.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 62 citations in OpenAlex.
- The immunoproteasome as a neuroimmune hub in the central nervous system: from proteostasis stress to inflammatory pathology.Journal of neuroinflammation · 2026Review
- A Systems Biology Approach to the Pathogenesis of Celiac Disease: Identification of Potential Protective and Promoting Mechanisms.Advanced biomedical research · 2024Article
- LMP2 deficiency causes abnormal metabolism, oxidative stress, neuroinflammation, myelin loss and neurobehavioral dysfunctions.Journal of translational medicine · 2023Article
- Mechanistic diversity in MHC class I antigen recognition.The Biochemical journal · 2021Review
- Article
- Genetic variations in theExperimental and therapeutic medicine · 2021Article
- Role of Proteasomes in Inflammation.Journal of clinical medicine · 2021Review
- Inhibition of the Immunoproteasome Subunit LMP7 Ameliorates Cerebral White Matter Demyelination Possibly via TGFEvidence-based complementary and alternative medicine : eCAM · 2021Article
- Review
- The impact of regional astrocyte interferon-γ signaling during chronic autoimmunity: a novel role for the immunoproteasome.Journal of neuroinflammation · 2020Article
- Proteolytic dynamics of human 20S thymoproteasome.The Journal of biological chemistry · 2019Article
- Article
- A Sentinel in the Crosstalk Between the Nervous and Immune System: The (Immuno)-Proteasome.Frontiers in immunology · 2019Review
- Islet stress, degradation and autoimmunity.Diabetes, obesity & metabolism · 2018Review
- The ubiquitin proteasome system as a potential therapeutic target for systemic sclerosis.Translational research : the journal of laboratory and clinical medicine · 2018Review
- Neuroinflammatory targets and treatments for epilepsy validated in experimental models.Epilepsia · 2017Review
- Emerging role of immunoproteasomes in pathophysiology.Immunology and cell biology · 2016Review
- Association Analysis of Proteasome Subunits and Transporter Associated with Antigen Processing on Chinese Patients with Parkinson's Disease.Chinese medical journal · 2016Article
- Proteasomes generate spliced epitopes by two different mechanisms and as efficiently as non-spliced epitopes.Scientific reports · 2016Article
- Ubiquitin-independent proteosomal degradation of myelin basic protein contributes to development of neurodegenerative autoimmunity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
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Authors and funding
23 authors at 10 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlbeit several studies pointed out the pivotal role that CD4+T cells have in Multiple Sclerosis, the CD8+ T cells involvement in the pathology is still in its early phases of investigation. Proteasome degradation is the key step in the production of MHC class I-restricted epitopes and therefore its activity could be an important element in the activation and regulation of autoreactive CD8+ T cells in Multiple Sclerosis. METHODOLOGY/PRINCIPAL
findingsImmunoproteasomes and PA28-alphabeta regulator are present in MS affected brain area and accumulated in plaques. They are expressed in cell types supposed to be involved in MS development such as neurons, endothelial cells, oligodendrocytes, macrophages/macroglia and lymphocytes. Furthermore, in a genetic study on 1262 Italian MS cases and 845 controls we observed that HLA-A*02+ female subjects carrying the immunoproteasome LMP2 codon 60HH variant have a reduced risk to develop MS. Accordingly, immunoproteasomes carrying the LMP2 60H allele produce in vitro a lower amount of the HLA-A*0201 restricted immunodominant epitope MBP(111-119). CONCLUSION/SIGNIFICANCE: The immunoproteasome LMP2 60HH variant reduces the risk to develop MS amongst Italian HLA-A*02+ females. We propose that such an effect is mediated by the altered proteasome-dependent production of a specific MBP epitope presented on the MHC class I. Our observations thereby support the hypothesis of an involvement of immunoproteasome in the MS pathogenesis.
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