Analysis of self-antigen specificity of islet-infiltrating T cells from human donors with type 1 diabetes (original) (raw)

Change history

In the version of this article initially published, the IA-2545–562 peptide identified as a target of a T cell clone was mislabeled as the native version of the peptide. The T cell clone responded to a modified version of the peptide with glutamine-to-glutamic-acid deaminations at positions 548, 551 and 556. The sentence, “From donor T1D.7, a CD4+ T cell clone recognized an IA-2 peptide with three glutamine-to-glutamic-acid deaminations (IA-2545–562(Q–G548,551,556); Fig. 2e)” has been added on p.1484 to reflect this. The relevant text has also been edited in the main text on p.1483; in Figure 2e and the Figure 2 legend; and in Figure 3b. Additionally, the phrase, ‘, a deaminated IA-2 peptide’ has been added after ‘…(a panel of 60 peptides)…’ to the ‘Peptides’ section of the Online Methods. Finally, in the Figure 2 legend, the phrase ‘Detection of reactivity to known autoreactive targets…’ has been changed to ‘Detection of reactivity to autoreactive targets…’. These errors have been corrected in the HTML and PDF versions of the article.

In the version of this article initially published online, the authors forgot to acknowledge the islet-isolation team at the Diabetes Research Institute, University of Miami. This oversight has been corrected for the print, PDF and HTML versions of this article.

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Acknowledgements

This research was performed with the support of the Network for Pancreatic Organ Donors with Diabetes (nPOD), a collaborative type 1 diabetes research project sponsored by the Juvenile Diabetes Research Foundation. Organ-procurement organizations (OPOs) partnering with nPOD to provide research resources are listed at http://www.jdrfnpod.org/for-partners/npod-partners/. We thank the families of the donors. We also thank M. Nakayama (Barbara Davis Center for Childhood Diabetes, University of Colorado) for supplying B cells from HLA-matched donors, and S. Purushothaman for her expert technical assistance. We thank D. Melton (Harvard University) for resources supporting this project. We thank G. Nepom, H. Reijonen (Benaroya Research Institute at Virginia Mason) and D. Hafler (Yale University) for providing B cell and T cell lines and clones. We also acknowledge the islet-isolation team at the Diabetes Research Institute, University of Miami. This study was supported by the University of Massachusetts Medical School Flow Cytometry Core Facility. The following funding sources supported this research: the Helmsley Charitable Trust 2015PG-T1D057 (S.C.K.), AI126189 (S.C.K.) and the Human Islet Research Network (HIRN) Opportunity Pool Fund U01 DK104162 (S.C.K.), DK089572 (A.C.P., D.M.H.), DK072473 (A.C.P.), DK104211 (A.C.P.), DK108120 (A.C.P.), DK106755 (A.C.P.), Islet Procurement and Analysis Core of the Vanderbilt Diabetes Research and Training Grant Center (DK020593) (A.C.P.), PO142288 (M.A., C. Mathews, M.C.T.), DK081166 (K.H.), Juvenile Diabetes Research Foundation 2-SRA-2015-68-Q-R (A.C.P., D.M.H.), 2-SRA-2015-52-Q-R (L.O., C. Mathieu), 2-SRA-2014-297-Q-R (E.A.J.), 25-2013-268 (M.A.A., with subcontract to J.S.K.), GOA 14/010 (L.O., C. Mathieu), American Diabetes Association Pathway to Stop Diabetes Grant 1-15-ACE-14 (T.D.), Helmsley Charitable Trust 2009PG-T1D006 (R.M.), Glass Charitable Foundation (R.M.) and the Helmsley Charitable Trust (George Eisenbarth nPOD Award for Team Science, 2015PG-T1D052 (A.P.)).

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Diabetes, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    Jenny Aurielle B Babon, Megan E DeNicola, David M Blodgett, David M Harlan & Sally C Kent
  2. Department of Clinical and Experimental Medicine, Laboratory for Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
    Inne Crèvecoeur, Lut Overbergh & Chantal Mathieu
  3. Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Thomas S Buttrick & Wassim Elyaman
  4. Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    René Maehr
  5. Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Pittsburgh, Pennsylvania, USA
    Rita Bottino
  6. Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA
    Rita Bottino
  7. Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Ali Naji
  8. Department of Information Sciences, Beckman Research Institute, City of Hope, Duarte, California, USA
    John Kaddis
  9. Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA
    Eddie A James
  10. Division of Diabetes, Department of Medicine, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Rachana Haliyur, Marcela Brissova & Alvin C Powers
  11. Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, Colorado, USA
    Thomas Delong & Kathryn Haskins
  12. Diabetes Research Institute, University of Miami, Miami, Florida, USA
    Alberto Pugliese
  13. Departments of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida, USA
    Martha Campbell-Thompson, Clayton Mathews & Mark A Atkinson
  14. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA
    Alvin C Powers
  15. Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA
    Alvin C Powers

Authors

  1. Jenny Aurielle B Babon
  2. Megan E DeNicola
  3. David M Blodgett
  4. Inne Crèvecoeur
  5. Thomas S Buttrick
  6. René Maehr
  7. Rita Bottino
  8. Ali Naji
  9. John Kaddis
  10. Wassim Elyaman
  11. Eddie A James
  12. Rachana Haliyur
  13. Marcela Brissova
  14. Lut Overbergh
  15. Chantal Mathieu
  16. Thomas Delong
  17. Kathryn Haskins
  18. Alberto Pugliese
  19. Martha Campbell-Thompson
  20. Clayton Mathews
  21. Mark A Atkinson
  22. Alvin C Powers
  23. David M Harlan
  24. Sally C Kent

Contributions

S.C.K., D.M.H. and J.A.B.B. designed the study. J.A.B.B., M.E.D., D.M.B. and S.C.K. performed experiments. T.S.B., W.E., R.H., M.B. and M.C.-T. performed experiments. R.M., I.C., E.A.J., L.O., C. Mathieu, T.D. and K.H. generated and supplied reagents. R.B., A.N., J.K., A.P., C. Mathews, M.A.A., M.B., R.H., A.C.P. and D.M.H. provided islets. S.C.K. wrote the manuscript, and all authors edited the manuscript.

Corresponding author

Correspondence toSally C Kent.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Tables and Figures

Supplementary Tables 1–3 and Supplementary Figures 1–4 Supplemental Table 1. Summary of characteristics and tally of CD4+ and CD8+ lines and clones derived from islats of donors with T1D. Supplemental Table 2. Summary of characteristics of normal donors (Is) without T1D and lack of islet infiltrating T cells. Supplemental Table 3. Islet equivalents (IEQ) recovered from six of the islet isolations from donors with T1D. Supplemental Figure 1. One hundred and two T cells lines grown from individual islets from donors with T1D were mixtures of CD4 and CD8 T cells. Supplemental Figure 2. DQ8 restriction and proinflammatory cytokine secretion of a CD4+ T cell line reactive with hybrid peptide hEGGG:NP-Y (GQVELGGG:SSPETLI). Supplemental Figure 3. Islet-derived autoreactive T cells are pro-inflammatory. Supplemental Figure 4. Autoreactive T cell clones recognize HLA-matched B cells transduced with autoantigen. (PDF 578 kb)

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Babon, J., DeNicola, M., Blodgett, D. et al. Analysis of self-antigen specificity of islet-infiltrating T cells from human donors with type 1 diabetes.Nat Med 22, 1482–1487 (2016). https://doi.org/10.1038/nm.4203

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