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Hybrid Insulin Peptides Are Autoantigens in Type 1 Diabetes

We recently established that hybrid insulin peptides (HIPs) are present in human islets and that T cells reactive to HIPs are found in the residual islets of organ donors with type 1 diabetes (T1D). Here, we investigate whether HIP-reactive T cells are indicative of ongoing autoimmunity in patients...

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Autores principales: Baker, Rocky L., Rihanek, Marynette, Hohenstein, Anita C., Nakayama, Maki, Michels, Aaron, Gottlieb, Peter A., Haskins, Kathryn, Delong, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702640/
https://www.ncbi.nlm.nih.gov/pubmed/31175101
http://dx.doi.org/10.2337/db19-0128
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author Baker, Rocky L.
Rihanek, Marynette
Hohenstein, Anita C.
Nakayama, Maki
Michels, Aaron
Gottlieb, Peter A.
Haskins, Kathryn
Delong, Thomas
author_facet Baker, Rocky L.
Rihanek, Marynette
Hohenstein, Anita C.
Nakayama, Maki
Michels, Aaron
Gottlieb, Peter A.
Haskins, Kathryn
Delong, Thomas
author_sort Baker, Rocky L.
collection PubMed
description We recently established that hybrid insulin peptides (HIPs) are present in human islets and that T cells reactive to HIPs are found in the residual islets of organ donors with type 1 diabetes (T1D). Here, we investigate whether HIP-reactive T cells are indicative of ongoing autoimmunity in patients with T1D. We used interferon-γ enzyme-linked immune absorbent spot analyses on peripheral blood mononuclear cells (PBMCs) to determine whether patients with new-onset T1D or control subjects displayed T-cell reactivity to a panel of 16 HIPs. We observed that nearly one-half of the patients responded to one or more HIPs. Responses to four HIPs were significantly elevated in patients with T1D but not in control subjects. To characterize the T cells reactive to HIPs, we used a carboxyfluorescein succinimidyl ester–based assay to clone T cells from PBMCs. We isolated six nonredundant, antigen-specific T-cell clones, most of which reacting to their target HIPs in the low nanomolar range. One T-cell clone was isolated from the same patient on two different blood draws, indicating persistence of this T-cell clone in the peripheral blood. This work suggests that HIPs are important target antigens in human subjects with T1D and may play a critical role in disease.
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spelling pubmed-67026402020-09-01 Hybrid Insulin Peptides Are Autoantigens in Type 1 Diabetes Baker, Rocky L. Rihanek, Marynette Hohenstein, Anita C. Nakayama, Maki Michels, Aaron Gottlieb, Peter A. Haskins, Kathryn Delong, Thomas Diabetes Immunology and Transplantation We recently established that hybrid insulin peptides (HIPs) are present in human islets and that T cells reactive to HIPs are found in the residual islets of organ donors with type 1 diabetes (T1D). Here, we investigate whether HIP-reactive T cells are indicative of ongoing autoimmunity in patients with T1D. We used interferon-γ enzyme-linked immune absorbent spot analyses on peripheral blood mononuclear cells (PBMCs) to determine whether patients with new-onset T1D or control subjects displayed T-cell reactivity to a panel of 16 HIPs. We observed that nearly one-half of the patients responded to one or more HIPs. Responses to four HIPs were significantly elevated in patients with T1D but not in control subjects. To characterize the T cells reactive to HIPs, we used a carboxyfluorescein succinimidyl ester–based assay to clone T cells from PBMCs. We isolated six nonredundant, antigen-specific T-cell clones, most of which reacting to their target HIPs in the low nanomolar range. One T-cell clone was isolated from the same patient on two different blood draws, indicating persistence of this T-cell clone in the peripheral blood. This work suggests that HIPs are important target antigens in human subjects with T1D and may play a critical role in disease. American Diabetes Association 2019-09 2019-06-07 /pmc/articles/PMC6702640/ /pubmed/31175101 http://dx.doi.org/10.2337/db19-0128 Text en © 2019 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
spellingShingle Immunology and Transplantation
Baker, Rocky L.
Rihanek, Marynette
Hohenstein, Anita C.
Nakayama, Maki
Michels, Aaron
Gottlieb, Peter A.
Haskins, Kathryn
Delong, Thomas
Hybrid Insulin Peptides Are Autoantigens in Type 1 Diabetes
title Hybrid Insulin Peptides Are Autoantigens in Type 1 Diabetes
title_full Hybrid Insulin Peptides Are Autoantigens in Type 1 Diabetes
title_fullStr Hybrid Insulin Peptides Are Autoantigens in Type 1 Diabetes
title_full_unstemmed Hybrid Insulin Peptides Are Autoantigens in Type 1 Diabetes
title_short Hybrid Insulin Peptides Are Autoantigens in Type 1 Diabetes
title_sort hybrid insulin peptides are autoantigens in type 1 diabetes
topic Immunology and Transplantation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702640/
https://www.ncbi.nlm.nih.gov/pubmed/31175101
http://dx.doi.org/10.2337/db19-0128
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