• An Erratum to this article was published on 13 September 2017

Abstract

Genetic studies have shown the association of Parkinson’s disease with alleles of the major histocompatibility complex1,2,3. Here we show that a defined set of peptides that are derived from α-synuclein, a protein aggregated in Parkinson’s disease4, 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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Acknowledgements

Supported by the JPB (D.S., T.M.D), William F. Richter (D.S.), Michael J. Fox (A.S., D.S.) and Parkinson’s Foundations (A.S., D.S.). X.M., V.L.D. and T.M.D. are supported by NIH/NINDS grant P50 NS38377. X.M. is supported by NIA ADRC P50AG005146. T.M.D. is the Abramson Professor. X.M., V.L.D. and T.M.D. acknowledge joint support by AHMMRF, JHH and JHUSOM Parkinson’s disease program, M-2014.

Author information

Affiliations

  1. Departments of Psychiatry, Columbia University, Division of Molcular Therapeutics, New York State Psychiatric Institute, New York, New York 10032, USA

    • David Sulzer
    • , Francesca Garretti
    • , Ellen Kanter
    • , Julian Agin-Liebes
    • , Elizabeth Phillips
    •  & Simon Mallal
  2. Department of Neurology, Columbia University, New York, New York 10032, USA

    • David Sulzer
    • , Roy N. Alcalay
    • , Lucien Cote
    • , Christopher Liong
    • , Elizabeth Phillips
    •  & Simon Mallal
  3. Department of Pharmacology, Columbia University, New York, New York 10032, USA

    • David Sulzer
  4. Department of Microbiology and Immunology, University of Oklahoma, Oklahoma City, Oklahoma 73104, USA

    • Curtis McMurtrey
    •  & William H. Hildebrand
  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

    • Xiaobo Mao
    • , Valina L. Dawson
    •  & Ted M. Dawson
  6. Adrienne Helis Malvin Medical Research Foundation, New Orleans, Louisiana 70130-2685, USA

    • Xiaobo Mao
    • , Valina L. Dawson
    •  & Ted M. Dawson
  7. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

    • Valina L. Dawson
  8. Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

    • Valina L. Dawson
    •  & Ted M. Dawson
  9. Department of Pharmacology & Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

    • Ted M. Dawson
  10. Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA

    • Carla Oseroff
    • , John Pham
    • , John Sidney
    • , Myles B. Dillon
    • , Chelsea Carpenter
    • , Daniela Weiskopf
    • , Bjoern Peters
    • , April Frazier
    • , Cecilia S. Lindestam Arlehamn
    •  & Alessandro Sette
  11. Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia 6150, Australia

    • Elizabeth Phillips
    •  & Simon Mallal
  12. Vanderbilt University School of Medicine, Nashville, Tennessee 37235, USA

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Contributions

D.S. and A.S. conceived the study and wrote the paper. C.S.L.A. and F.G. contributed to writing and prepared figures. R.N.A. and L.C. recruited participants and performed clinical evaluations. C.L., J.A.-L. and A.F. maintained patient data and assisted in subject recruitment. E.K. arranged tissue handling and maintained records. F.G., C.O., J.P., M.B.D., C.C., D.W., E.P., S.M., B.P., W.H.H., C.M. and C.S.L.A. conducted analyses of T cells and antigenic epitopes. X.M., V.L.D. and T.M.D. prepared and characterized α-syn proteins and fibrils. J.S. performed in vitro MHC-binding assays.

Competing interests

Columbia University filed a patent application for the use of α-syn peptides as biomarkers (US patent application number 15/300,713). D.S. (Columbia University) and A.S. (La Jolla Institute for Allergy and Immunology) are listed as inventors.

Corresponding authors

Correspondence to David Sulzer or Alessandro Sette.

Reviewer Information Nature thanks M. Tansey and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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https://doi.org/10.1038/nature22815

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