Ghent University Academic Bibliography

Advanced

Incidental CD8 T cell reactivity against caspase-cleaved apoptotic self-antigens from ubiquitously expressed proteins in islets from prediabetic human leucocyte antigen-A2 transgenic non-obese diabetic mice

Ken Coppieters UGent, N Amirian and MG von Herrath (2011) CLINICAL AND EXPERIMENTAL IMMUNOLOGY. 165(2). p.155-162
abstract
Apoptosis is known as a major mechanism which contributes to beta cell decay in type 1 diabetes. Commitment to this pathway generally involves caspase-mediated protein cleavage and was found to induce cross-presentation of a specific antigen repertoire under certain inflammatory conditions. We aimed to assess the significance of the CD8 T cell population reactive against such caspase-cleaved apoptotic self-antigens in pancreatic islets of prediabetic human leucocyte antigen (HLA)-A2 transgenic non-obese diabetic chimeric monochain transgene construct (NOD.HHD) mice. We have reproduced a unique peptide library consisting of human CD8 T cell-derived apoptosis-specific antigens, all of which belong to structural proteins expressed ubiquitously in human islets. Pancreatic islets from prediabetic NOD.HHD mice, harbouring humanized major histocompatibilty complex (MHC) class I, were isolated and handpicked at various ages, and islet-infiltrating CD8 T cells were expanded in vitro and used as responders in an interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) assay. Human T2 cells were used as antigen-presenting cells (APC) to avoid endogenous antigen presentation. Analogous to the interindividual variability found with peptides from known islet autoantigens such as islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) and insulin, some mice showed variable, low-degree CD8 T cell reactivity against caspase-cleaved self-antigens. Because reactivity was predominantly minor and often undetectable, we conclude that beta cell apoptosis does not routinely provoke the development of dominant cytotoxic T lymphocyte (CTL) reactive against caspase-cleaved self-antigens in the NOD.HHD model.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
AUTOANTIGEN IA-2, NOD MICE, DENDRITIC CELLS, EPITOPE, HLA-A-ASTERISK-0201, IDENTIFICATION, AUTOIMMUNITY, apoptosis, CD8 T cells, diabetes, epitope spreading, humanized mice, VIMENTIN INTERMEDIATE FILAMENTS, GLUTAMIC-ACID DECARBOXYLASE, PANCREATIC BETA-CELLS
journal title
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Clin. Exp. Immunol.
volume
165
issue
2
pages
155 - 162
Web of Science type
Article
Web of Science id
000292338200003
JCR category
IMMUNOLOGY
JCR impact factor
3.36 (2011)
JCR rank
53/138 (2011)
JCR quartile
2 (2011)
ISSN
0009-9104
DOI
10.1111/j.1365-2249.2011.04420.x
language
English
UGent publication?
no
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2120280
handle
http://hdl.handle.net/1854/LU-2120280
date created
2012-05-30 10:01:14
date last changed
2012-06-07 13:28:31
@article{2120280,
  abstract     = {Apoptosis is known as a major mechanism which contributes to beta cell decay in type 1 diabetes. Commitment to this pathway generally involves caspase-mediated protein cleavage and was found to induce cross-presentation of a specific antigen repertoire under certain inflammatory conditions. We aimed to assess the significance of the CD8 T cell population reactive against such caspase-cleaved apoptotic self-antigens in pancreatic islets of prediabetic human leucocyte antigen (HLA)-A2 transgenic non-obese diabetic chimeric monochain transgene construct (NOD.HHD) mice. We have reproduced a unique peptide library consisting of human CD8 T cell-derived apoptosis-specific antigens, all of which belong to structural proteins expressed ubiquitously in human islets. Pancreatic islets from prediabetic NOD.HHD mice, harbouring humanized major histocompatibilty complex (MHC) class I, were isolated and handpicked at various ages, and islet-infiltrating CD8 T cells were expanded in vitro and used as responders in an interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) assay. Human T2 cells were used as antigen-presenting cells (APC) to avoid endogenous antigen presentation. Analogous to the interindividual variability found with peptides from known islet autoantigens such as islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) and insulin, some mice showed variable, low-degree CD8 T cell reactivity against caspase-cleaved self-antigens. Because reactivity was predominantly minor and often undetectable, we conclude that beta cell apoptosis does not routinely provoke the development of dominant cytotoxic T lymphocyte (CTL) reactive against caspase-cleaved self-antigens in the NOD.HHD model.},
  author       = {Coppieters, Ken and Amirian, N and von Herrath, MG},
  issn         = {0009-9104},
  journal      = {CLINICAL AND EXPERIMENTAL IMMUNOLOGY},
  keyword      = {AUTOANTIGEN IA-2,NOD MICE,DENDRITIC CELLS,EPITOPE,HLA-A-ASTERISK-0201,IDENTIFICATION,AUTOIMMUNITY,apoptosis,CD8 T cells,diabetes,epitope spreading,humanized mice,VIMENTIN INTERMEDIATE FILAMENTS,GLUTAMIC-ACID DECARBOXYLASE,PANCREATIC BETA-CELLS},
  language     = {eng},
  number       = {2},
  pages        = {155--162},
  title        = {Incidental CD8 T cell reactivity against caspase-cleaved apoptotic self-antigens from ubiquitously expressed proteins in islets from prediabetic human leucocyte antigen-A2 transgenic non-obese diabetic mice},
  url          = {http://dx.doi.org/10.1111/j.1365-2249.2011.04420.x},
  volume       = {165},
  year         = {2011},
}

Chicago
Coppieters, Ken, N Amirian, and MG von Herrath. 2011. “Incidental CD8 T Cell Reactivity Against Caspase-cleaved Apoptotic Self-antigens from Ubiquitously Expressed Proteins in Islets from Prediabetic Human Leucocyte antigen-A2 Transgenic Non-obese Diabetic Mice.” Clinical and Experimental Immunology 165 (2): 155–162.
APA
Coppieters, K., Amirian, N., & von Herrath, M. (2011). Incidental CD8 T cell reactivity against caspase-cleaved apoptotic self-antigens from ubiquitously expressed proteins in islets from prediabetic human leucocyte antigen-A2 transgenic non-obese diabetic mice. CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 165(2), 155–162.
Vancouver
1.
Coppieters K, Amirian N, von Herrath M. Incidental CD8 T cell reactivity against caspase-cleaved apoptotic self-antigens from ubiquitously expressed proteins in islets from prediabetic human leucocyte antigen-A2 transgenic non-obese diabetic mice. CLINICAL AND EXPERIMENTAL IMMUNOLOGY. 2011;165(2):155–62.
MLA
Coppieters, Ken, N Amirian, and MG von Herrath. “Incidental CD8 T Cell Reactivity Against Caspase-cleaved Apoptotic Self-antigens from Ubiquitously Expressed Proteins in Islets from Prediabetic Human Leucocyte antigen-A2 Transgenic Non-obese Diabetic Mice.” CLINICAL AND EXPERIMENTAL IMMUNOLOGY 165.2 (2011): 155–162. Print.