T cells from patients with Parkinson's disease recognize α-synuclein peptides

David Sulzer; Roy N Alcalay; Francesca Garretti; Lucien Cote; Ellen Kanter; Julian Agin-Liebes; Christopher Liong; Curtis McMurtrey; William H Hildebrand; Xiaobo Mao; Valina L Dawson; Ted M Dawson; Carla Oseroff; John Pham; John Sidney; Myles B Dillon; Chelsea Carpenter; Daniela Weiskopf; Elizabeth Phillips; Simon Mallal; Bjoern Peters; April Frazier; Cecilia S Lindestam Arlehamn; Alessandro Sette

doi:10.1038/nature22815

T cells from patients with Parkinson's disease recognize α-synuclein peptides

Nature. 2017 Jun 29;546(7660):656-661. doi: 10.1038/nature22815. Epub 2017 Jun 21.

Authors

David Sulzer^{1

2

3}, Roy N Alcalay², Francesca Garretti¹, Lucien Cote², Ellen Kanter¹, Julian Agin-Liebes¹, Christopher Liong², Curtis McMurtrey⁴, William H Hildebrand⁴, Xiaobo Mao^{5

6}, Valina L Dawson^{5

6

7

8}, Ted M Dawson^{5

6

8

9}, Carla Oseroff¹⁰, John Pham¹⁰, John Sidney¹⁰, Myles B Dillon¹⁰, Chelsea Carpenter¹⁰, Daniela Weiskopf¹⁰, Elizabeth Phillips^{11

1

2}, Simon Mallal^{11

1

2}, Bjoern Peters¹⁰, April Frazier¹⁰, Cecilia S Lindestam Arlehamn¹⁰, Alessandro Sette¹⁰

Affiliations

¹ Departments of Psychiatry, Columbia University, Division of Molcular Therapeutics, New York State Psychiatric Institute, New York, New York 10032, USA.
² Department of Neurology, Columbia University, New York, New York 10032, USA.
³ Department of Pharmacology, Columbia University, New York, New York 10032, USA.
⁴ Department of Microbiology and Immunology, University of Oklahoma, Oklahoma City, Oklahoma 73104, USA.
⁵ Neuroregeneration and Stem Cell Program, Institute for Cell Engineering and the Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
⁶ Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana 70130-2685, USA.
⁷ Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
⁸ Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
⁹ Department of Pharmacology &Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
¹⁰ Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
¹¹ Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia 6150, Australia.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alleles
Amino Acid Sequence
Autoimmunity
Epitopes, T-Lymphocyte / immunology
Female
HLA Antigens / genetics
HLA Antigens / immunology
Humans
Male
Middle Aged
Parkinson Disease / genetics
Parkinson Disease / immunology*
Parkinson Disease / pathology
Peptide Fragments / chemistry
Peptide Fragments / immunology
T-Lymphocytes / immunology*
T-Lymphocytes / pathology
T-Lymphocytes, Cytotoxic / immunology
T-Lymphocytes, Cytotoxic / pathology
T-Lymphocytes, Helper-Inducer / immunology
T-Lymphocytes, Helper-Inducer / pathology
alpha-Synuclein / chemistry
alpha-Synuclein / immunology*

Substances

Epitopes, T-Lymphocyte
HLA Antigens
Peptide Fragments
alpha-Synuclein

Abstract

Publication types

MeSH terms

Substances

Grants and funding