T cells from patients with Parkinson’s disease recognize α-synuclein peptides
Open accessAbstract
Genetic studies have shown the association of Parkinson's disease with alleles of the major histocompatibility complex. Here we show that a defined set of peptides that are derived from α-synuclein, a protein aggregated in Parkinson's disease, act as antigenic epitopes displayed by these alleles and drive helper and cytotoxic T cell responses in patients with Parkinson's disease. These responses may explain the association of Parkinson's disease with specific major histocompatibility complex alleles.
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Adaptive immune system plays an important role in approximately 40% of PD.
“Recently, numerous evidences suggest that adaptive immune system plays important role in approximately 40% PD.”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [74]
The paper reports that approximately 40% of PD participants in its cohort had immune responses to α-synuclein epitopes and says that evidence suggests a role for acquired immunity. It does not establish that the adaptive immune system plays an important role in approximately 40% of all people with PD; the percentage describes an observed response in this cohort. (LLM, conf=0.85)
Experimental — accuracy not yet measuredHigh number of T cells response to α-synuclein were found in brain of PD patients and mouse model.
“A high number of T cells response to α-synuclein were found in the brain of PD patients and mouse model.”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [74]
The main text reports α-synuclein-reactive T cells in patients with Parkinson’s disease, and Extended Data Figure 1 measures responses in peripheral blood cells—not in brain tissue. The paper also mentions T-cell responses in mice from prior studies, but it does not establish a high number of α-synuclein-reactive T cells in the brains of either patients or mouse models. The indexed passages provide section labels but no page numbers. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMicroglia activation by α-synuclein aggregates or other factors can increase MHC I expression on neurons, enhance presentation of α-synuclein antigens by neurons, which are subsequently killed by α-synuclein reactive T cells.
“Microglia activation by α-synuclein aggregates or other factors can increase the expression of MHC I expression on neurons, enhance the presentation of α-synuclein antigens by neurons, which were subsequently killed by α-synuclein reactive T cells.74–76”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [74]
The passage labeled Abstract (page unavailable) reports that α-synuclein-activated microglia can induce MHC class I expression on substantia nigra dopamine neurons, and that CD8+ T cells can kill neurons presenting an appropriate MHC I–peptide combination. The paper also reports α-synuclein-reactive T cells in patients, but these passages do not establish that neurons present α-synuclein peptides and are subsequently killed by those specific T cells. (LLM, conf=0.88)
Experimental — accuracy not yet measuredT cells can recognize certain alpha-synuclein antigenic epitopes, and this is largely mediated by CD4+ T cells and CD8+ T cells in patients with Parkinson's disease.
“T cells can recognize certain a-synuclein antigenic epitopes, and this is largely mediated by CD4 + T cells and CD8 + T cells in patients with Parkinson's disease.94”
From The role of gut dysbiosis in Parkinson’s disease: mechanistic insights and therapeutic options (2021) · cites this paper as [94]
The passage describing responses in nine Parkinson’s disease participants (section labeled Abstract) confirms that T cells recognized α-synuclein antigenic peptides. It says responses were largely mediated by CD4+ T cells, with potential CD8+ contributions; CD8+ cells mediated most of the response in only one participant. The claim overstates the CD8+ role by presenting both cell types as largely mediating the response. (LLM, conf=0.89)
Experimental — accuracy not yet measuredThe deposition of α-syn protein fibrils into larger aggregates such as Lewy bodies or neurites has been associated with strong immunogenic responses in affected tissues of several neurodegenerative diseases.
“The deposition of α-syn protein fibrils into larger aggregates such as Lewy bodies or neurites has been associated with strong immunogenic responses in affected tissues of several neurodegenerative diseases (75, 93–97).”
From Mouse α-synuclein fibrils are structurally and functionally distinct from human fibrils associated with Lewy body diseases (2024) · cites this paper as [93]
The Abstract (page unavailable) describes α-synuclein aggregates in Parkinson’s disease Lewy bodies and reports immune responses to α-synuclein peptides, including responses to epitopes processed from fibrilized protein. It does not establish that fibril deposition produces strong immune responses in affected tissues across several neurodegenerative diseases; it explicitly says the role of these epitopes in additional synucleinopathies is untested. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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CD4 T Cells Induce A Subset of MHCII-Expressing Microglia that Attenuates Alzheimer Pathology
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T cell infiltration in both human multiple system atrophy and a novel mouse model of the disease
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Lower Lymphocyte Count is Associated With Increased Risk of Parkinson's Disease
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“In addition, heightened numbers of partially α-synuclein-reactive Th17 cells were discovered in the blood of PD patients (Sulzer et al., 2017); to the degree that PD has been postulated as an α-synuclein-reactive autoimmune disease (Benner et al., 2008; Hu, 2011).”
BackgroundExploring Human-Genome Gut-Microbiome Interaction in Parkinson’s Disease
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The role of immune-mediated alterations and disorders in ALS disease
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Age-Related Adaptive Immune Changes in Parkinson’s Disease
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- Authors
- Sulzer, D., Alcalay, R. N., Garretti, F., Cote, L., Kanter, E., Agin-Liebes, J., Liong, C., McMurtrey, C., Hildebrand, W. H., Mao, X., Dawson, V. L., Dawson, T. M., Oseroff, C., Pham, J., Sidney, J., Dillon, M. B., Carpenter, C., Weiskopf, D., Phillips, E., Mallal, S., Peters, B., Frazier, A., Lindestam Arlehamn, C. S., & Sette, A.
- Affiliations
- New York State Psychiatric Institute (US)
- Columbia University (US)
- University of Oklahoma (US)
- Johns Hopkins University (US)
- La Jolla Institute for Immunology (US)
- Murdoch University (AU)
- Corresponding author
- Sulzer, David
- Sette, Alessandro
- ORCID
- Venue
- Nature
- Published
- 2017-06-21
- Volume
- 546
- Issue
- 7660
- Pages
- 656-661
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5626019
- OpenAlex
- W2638382976
- Cited by
- 866
- References
- 44
- Citations by year
- 2026: 80 · 2025: 89 · 2024: 106 · 2023: 96 · 2022: 119 · 2021: 110 · 2020: 107 · 2019: 83 · 2018: 59 · 2017: 16
- FWCI
- 50.02
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-09-14)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Murdoch University Research Portal (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute on Aging (P50AG005146)
- National Institute of Neurological Disorders and Stroke (K02NS080915, R37NS067525, P50NS038377)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- Parkinson's disease, alpha-synuclein, T cell epitopes, CD4+ T cells, CD8+ cytotoxic T lymphocytes, MHC class I alleles, autoimmunity, substantia nigra, neurodegeneration
- MeSH terms
- Aged, Aged, 80 and over, Alleles, Amino Acid Sequence, Female, T-Lymphocytes, Helper-Inducer, HLA Antigens, Humans, Male, Middle Aged, Parkinson Disease, Peptide Fragments, T-Lymphocytes, T-Lymphocytes, Cytotoxic, Autoimmunity, Epitopes, T-Lymphocyte, alpha-Synuclein
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