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Weak Proinsulin Peptide–Major Histocompatibility Complexes Are Targeted in Autoimmune Diabetes in Mice
OBJECTIVE—Weak major histocompatibility complex (MHC) binding of self-peptides has been proposed as a mechanism that may contribute to autoimmunity by allowing for escape of autoreactive T-cells from the thymus. We examined the relationship between the MHC-binding characteristics of a β-cell antigen...
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Formato: | Texto |
Lenguaje: | English |
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American Diabetes Association
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453633/ https://www.ncbi.nlm.nih.gov/pubmed/18398138 http://dx.doi.org/10.2337/db08-0068 |
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author | Levisetti, Matteo G. Lewis, Danna M. Suri, Anish Unanue, Emil R. |
author_facet | Levisetti, Matteo G. Lewis, Danna M. Suri, Anish Unanue, Emil R. |
author_sort | Levisetti, Matteo G. |
collection | PubMed |
description | OBJECTIVE—Weak major histocompatibility complex (MHC) binding of self-peptides has been proposed as a mechanism that may contribute to autoimmunity by allowing for escape of autoreactive T-cells from the thymus. We examined the relationship between the MHC-binding characteristics of a β-cell antigen epitope and T-cell autoreactivity in a model of autoimmune diabetes. RESEARCH DESIGN AND METHODS—The binding of a proinsulin epitope, proinsulin-1(47–64) (PI-1[47–64]), to the MHC class II molecules I-A(g7) and I-A(k) was measured using purified class II molecules. T-cell reactivity to the proinsulin epitope was examined in I-A(g7+) and I-A(k+) mice. RESULTS—C-peptide epitopes bound very weakly to I-A(g7) molecules. However, C-peptide–reactive T-cells were induced after immunization in I-A(g7)–bearing mice (NOD and B6.g7) but not in I-A(k)–bearing mice (B10.BR and NOD.h4). T-cells reactive with the PI-1(47–64) peptide were found spontaneously in the peripancreatic lymph nodes of pre-diabetic NOD mice. These T-cells were activated by freshly isolated β-cells in the presence of antigen-presenting cells and caused diabetes when transferred into NOD.scid mice. CONCLUSIONS—These data demonstrate an inverse relationship between self-peptide–MHC binding and T-cell autoreactivity for the PI-1(47–64) epitope in autoimmune diabetes. |
format | Text |
id | pubmed-2453633 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-24536332009-07-01 Weak Proinsulin Peptide–Major Histocompatibility Complexes Are Targeted in Autoimmune Diabetes in Mice Levisetti, Matteo G. Lewis, Danna M. Suri, Anish Unanue, Emil R. Diabetes Immunology and Transplantation OBJECTIVE—Weak major histocompatibility complex (MHC) binding of self-peptides has been proposed as a mechanism that may contribute to autoimmunity by allowing for escape of autoreactive T-cells from the thymus. We examined the relationship between the MHC-binding characteristics of a β-cell antigen epitope and T-cell autoreactivity in a model of autoimmune diabetes. RESEARCH DESIGN AND METHODS—The binding of a proinsulin epitope, proinsulin-1(47–64) (PI-1[47–64]), to the MHC class II molecules I-A(g7) and I-A(k) was measured using purified class II molecules. T-cell reactivity to the proinsulin epitope was examined in I-A(g7+) and I-A(k+) mice. RESULTS—C-peptide epitopes bound very weakly to I-A(g7) molecules. However, C-peptide–reactive T-cells were induced after immunization in I-A(g7)–bearing mice (NOD and B6.g7) but not in I-A(k)–bearing mice (B10.BR and NOD.h4). T-cells reactive with the PI-1(47–64) peptide were found spontaneously in the peripancreatic lymph nodes of pre-diabetic NOD mice. These T-cells were activated by freshly isolated β-cells in the presence of antigen-presenting cells and caused diabetes when transferred into NOD.scid mice. CONCLUSIONS—These data demonstrate an inverse relationship between self-peptide–MHC binding and T-cell autoreactivity for the PI-1(47–64) epitope in autoimmune diabetes. American Diabetes Association 2008-07 /pmc/articles/PMC2453633/ /pubmed/18398138 http://dx.doi.org/10.2337/db08-0068 Text en Copyright © 2008, American Diabetes Association https://creativecommons.org/licenses/by-nc-nd/3.0/Readers 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. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Immunology and Transplantation Levisetti, Matteo G. Lewis, Danna M. Suri, Anish Unanue, Emil R. Weak Proinsulin Peptide–Major Histocompatibility Complexes Are Targeted in Autoimmune Diabetes in Mice |
title | Weak Proinsulin Peptide–Major Histocompatibility Complexes Are Targeted in Autoimmune Diabetes in Mice |
title_full | Weak Proinsulin Peptide–Major Histocompatibility Complexes Are Targeted in Autoimmune Diabetes in Mice |
title_fullStr | Weak Proinsulin Peptide–Major Histocompatibility Complexes Are Targeted in Autoimmune Diabetes in Mice |
title_full_unstemmed | Weak Proinsulin Peptide–Major Histocompatibility Complexes Are Targeted in Autoimmune Diabetes in Mice |
title_short | Weak Proinsulin Peptide–Major Histocompatibility Complexes Are Targeted in Autoimmune Diabetes in Mice |
title_sort | weak proinsulin peptide–major histocompatibility complexes are targeted in autoimmune diabetes in mice |
topic | Immunology and Transplantation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453633/ https://www.ncbi.nlm.nih.gov/pubmed/18398138 http://dx.doi.org/10.2337/db08-0068 |
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