Autoantigens Discovery and Characterization in Type 1 Diabetes

Event Details

Background

Type 1 diabetes is an autoimmune disease that is thought to be caused, in part, by a T cell-mediated destruction of insulin-producing β cells. High risk for disease, in those with genetic susceptibility, is predicted by the presence of two or more autoantibodies with different specificities. Autoantibodies against insulin, GAD65, IA-2, and ZnT8 are commonly known as the major specificities in type 1 diabetes. Despite this knowledge, we still do not know what leads to the breakdown of tolerance, and we have a poor understanding of type 1 diabetes etiology and pathophysiology. Several new autoantibodies have been recently discovered using innovative technologies, but neither their potential utility in monitoring disease development and treatment nor their role in the pathophysiology and etiology of type 1 diabetes has been explored.

The occurrence of post-translationally modified proteins (neoantigens) in autoimmune diseases such as rheumatoid arthritis and celiac disease is well documented. It was recently discovered that some T-cells in mouse models, as well as in people with type 1 diabetes, recognize neoantigens. If these altered self-proteins do not occur in the thymus, or are in other ways shielded from normal processes of peripheral self-tolerance, autoreactive T cells that recognize these peptides could be important for pathogenesis in type 1 diabetes. In addition, the endocrine function of the β cell and all its attendant processes, together with the pancreatic milieu, are increasingly thought to be associated with mechanisms of post-translational modification (for example, ER stress and microbiome interactions). Thus, continued identification and characterization of type 1 diabetes-relevant antigen epitopes for both autoantibodies and T cells is critically important for understanding the etiology and pathophysiology of type 1 diabetes. Characterization of these autoantigens could also bring new insights into the role of the islet autoimmunity in type 2 diabetes. Powerful new technologies provide opportunities to facilitate a more complete discovery and characterization of autoantigens, including hybrid peptides and post-translational modifications, and the immune response to them.

Meeting Objectives

One of the goals of this workshop is to bring together investigators that use new methods and technologies to identify autoantigens and responses to them (antibodies or T cells). Researchers with diverse expertise will share ideas and identify resources. This could help them uncover opportunities to work together, to accelerate the progress of antigen/antigen response discovery and detection. The workshop could also bring in expertise to advise on next steps and help discoveries transition to utility as biomarkers of disease progression, treatment response, and ultimately, new antigen specific therapeutics.

Another goal of the workshop is to have a discussion on the progress and potential future development for: 1) The identification of new autoantigens and epitopes in type 1 diabetes; 2) The characterization of the response to new and previously known antigens (T-cell or humoral); and 3) The use of these antigens/epitopes and their response for identifying disease triggers and mechanisms, monitoring disease progression, and developing new treatments or preventative vaccines.

Registration Deadline

October 15, 2017

This meeting is being held in conjunction with the Workshop on Immune System Engineering for Targeted Tolerance in Type 1 Diabetes (T1D).

Agenda

October 31, 2017

5:30 p.m. – 5:35 p.m.

Call to order and Introduction
Salvatore Sechi, NIDDK, NIH

5:35 p.m. – 6:30 p.m.

Key note lecture
Åke Lernmark, Lund University, Sweden

6:30 p.m. – 8:00 p.m.

Dinner at TBA

November 1, 2017

8:25 a.m. – 8:30 a.m.

Call to order

Session I: The characterization of the response to new and previously known antigens in Type 1 Diabetes and in different disease contexts (T-cell or humoral)

Chair: Teresa DiLorenzo, Albert Einstein College of Medicine

8:30 a.m. – 9:10 a.m.

The autoimmune response in T1D—What we know and what we don’t know
Teresa DiLorenzo, Albert Einstein College of Medicine

9:10 a.m. – 9:35 a.m.

Self-antigen specificity of islet-infiltrating T cells from human donors with type 1 diabetes
Sally C. Kent, University of Massachusetts Medical School

9:35 a.m. – 9:50 a.m.

Break

9:50 a.m. – 10:15 a.m.

Post-translational modifications and neo-epitopes in autoimmune rheumatoid arthritis
René E. M. Toes, Leiden University Medical Center

10:15 a.m. – 10:40 a.m.

T-Cell response in Cancer and Cancer immunotherapy
James Yang, NCI/NIH

10:40 a.m. – 11:05 a.m.

Autoimmunity in Type 2 Diabetes
Jerry Palmer, University of Washington

11:05 a.m. – 11:35 a.m.

Discussion Panel
Chair: Bart Roep
Panelists: Åke Lernmark, Teresa DiLorenzo, Sally C. Kent, René E. M. Toes, James Yang, Jerry Palmer

Session II: The identification of new autoantigens and epitopes in type 1 diabetes

Chair: Anthony Purcell, Monash University, Australia

11:35 a.m. – 12:15 p.m.

The state of the arts in the characterization of the humoral and T-cell responses
Anthony Purcell, Monash University, Australia

12:15 p.m. – 1:00 p.m.

Lunch (45 min)
Please familiarize yourself with local food options. Many are within walking distance.

1:00 p.m. – 1:25 p.m.

Discovery of New T1D Autoantigens Using “Epitope Surrogate” Technology
Thomas Kodadek, The Scripps Research Institute

1:25 p.m. – 1:50 p.m.

Post-Translational Modifications in T1D Pathogenesis
Bart Roep, Beckman Research Institute of City of Hope City of Hope

1:50 p.m. – 2:15 p.m.

Insulin Hybrid Peptides and their elicited Humoral and T-cell responses in Type 1 Diabetes
Kate Haskins, University of Colorado

2:15 p.m. – 2:30 p.m.

Neoantigens and their characterization in Type 1 Diabetes
Eddie James, Benaroya Research Institute

2:30 p.m. – 3:00 p.m.

Discussion Panel
Chair: Mark Peakman, King’s College
Panelists: Anthony Purcell, Thomas Kodadek, Bart Roep, Kate Haskins, Eddie James

3:00 p.m. – 3:15 p.m.

Break

Session III: Novel Technologies in T-Cell response and Autoantigen identification and Characterization

Chair: Thomas DeLong, University of Colorado

3:15 p.m. – 3:40 p.m.

Novel technologies to interrogate T cell recognition
Sine Reker Hadrup, Technical University of Denmark

3:40 p.m. – 4:05 p.m.

MHC-peptide-TCR interaction in autoimmunity
Larry Stern, U Mass Worcester

4:05 p.m. – 4:30 p.m.

Self antigenic peptides produced by proteasome-catalyzed peptide splicing
Michele Mishto, Universitätsmedizin Berlin Charite, Germany

4:30 p.m. – 4:45 p.m.

Single-cell analysis by mass cytometry for dissecting immune responses
Matthew H. Spitzer, UCSF

4:45 p.m. – 5:00 p.m.

The Immuno Epitope Database and computational challenges in new epitope discovery
Bjoern Peters, La Jolla Institute for Allergy and Immunology

5:00 p.m. – 5:30 p.m.

Discussion Panel
Chair: Thomas DeLong
Panelists: Sine Reker Hadrup, Larry Stern, Michele Mishto, Matthew H. Spitzer, Bjoern Peters

5:30 p.m. – 5:45 p.m.

Adjourn

5:45 p.m. – 6:30 p.m.

Keynote talk from next day workshop

6:30 p.m.

Dinner