Spontaneous peripheral T-cell responses to the IA-2β (phogrin) autoantigen in young nonobese diabetic mice

Peter Achenbach, Katalin Kelemen, Dale R. Wegmann, John C. Hutton

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Phogrin (IA-2β), a major autoantigen in type 1 diabetes in man is recognized by peripheral T cells in the nonobese diabetic (NOD) mouse. CD4+ T-cell clones derived from immunized NOD animals elicit islet destruction in a disease transfer model. Spontaneous proliferative responses to the protein and derived peptide epitopes were detected in peripheral lymph node cells (LNC) of unprimed NOD mice but not BALB/c controls as early as 4 weeks of age at a time point when insulitis in NOD animals is minimal. Responses to irradiated NOD islet cells but not irradiated NOD spleen cells were observed for both male and female NOD animals. Insulin, phogrin and phogrin-peptide 7 (aa 755-777) but not phogrin-peptide 2 (aa 640-659) or tetanus toxin peptide were recognized as antigens. Islet cell-reactive and phogrin peptide 7-specific CD4+ T-cell lines were generated from splenocytes of unprimed 4-week-old NOD females and shown to secrete Th1-type cytokines. The results show that the phogrin molecule is targeted early in the course of disease in NOD animals at a time when circulating autoantibodies are absent and insulitis is minimal.

Original languageEnglish (US)
Pages (from-to)111-116
Number of pages6
JournalJournal of Autoimmunity
Volume19
Issue number3
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Fingerprint

Inbred NOD Mouse
Autoantigens
T-Lymphocytes
Peptides
Islets of Langerhans
Tetanus Toxin
Type 1 Diabetes Mellitus
Autoantibodies
Epitopes
Spleen
Clone Cells
Lymph Nodes
Insulin
Cytokines
Antigens
Cell Line
Proteins

Keywords

  • Autoantigen
  • Diabetes
  • IA-2β
  • NOD mouse
  • T-cell response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Spontaneous peripheral T-cell responses to the IA-2β (phogrin) autoantigen in young nonobese diabetic mice. / Achenbach, Peter; Kelemen, Katalin; Wegmann, Dale R.; Hutton, John C.

In: Journal of Autoimmunity, Vol. 19, No. 3, 01.01.2002, p. 111-116.

Research output: Contribution to journalArticle

@article{4ecd6d0875fc4d1e934ab61d258c25ea,
title = "Spontaneous peripheral T-cell responses to the IA-2β (phogrin) autoantigen in young nonobese diabetic mice",
abstract = "Phogrin (IA-2β), a major autoantigen in type 1 diabetes in man is recognized by peripheral T cells in the nonobese diabetic (NOD) mouse. CD4+ T-cell clones derived from immunized NOD animals elicit islet destruction in a disease transfer model. Spontaneous proliferative responses to the protein and derived peptide epitopes were detected in peripheral lymph node cells (LNC) of unprimed NOD mice but not BALB/c controls as early as 4 weeks of age at a time point when insulitis in NOD animals is minimal. Responses to irradiated NOD islet cells but not irradiated NOD spleen cells were observed for both male and female NOD animals. Insulin, phogrin and phogrin-peptide 7 (aa 755-777) but not phogrin-peptide 2 (aa 640-659) or tetanus toxin peptide were recognized as antigens. Islet cell-reactive and phogrin peptide 7-specific CD4+ T-cell lines were generated from splenocytes of unprimed 4-week-old NOD females and shown to secrete Th1-type cytokines. The results show that the phogrin molecule is targeted early in the course of disease in NOD animals at a time when circulating autoantibodies are absent and insulitis is minimal.",
keywords = "Autoantigen, Diabetes, IA-2β, NOD mouse, T-cell response",
author = "Peter Achenbach and Katalin Kelemen and Wegmann, {Dale R.} and Hutton, {John C.}",
year = "2002",
month = "1",
day = "1",
doi = "10.1006/jaut.2002.0611",
language = "English (US)",
volume = "19",
pages = "111--116",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Spontaneous peripheral T-cell responses to the IA-2β (phogrin) autoantigen in young nonobese diabetic mice

AU - Achenbach, Peter

AU - Kelemen, Katalin

AU - Wegmann, Dale R.

AU - Hutton, John C.

PY - 2002/1/1

Y1 - 2002/1/1

N2 - Phogrin (IA-2β), a major autoantigen in type 1 diabetes in man is recognized by peripheral T cells in the nonobese diabetic (NOD) mouse. CD4+ T-cell clones derived from immunized NOD animals elicit islet destruction in a disease transfer model. Spontaneous proliferative responses to the protein and derived peptide epitopes were detected in peripheral lymph node cells (LNC) of unprimed NOD mice but not BALB/c controls as early as 4 weeks of age at a time point when insulitis in NOD animals is minimal. Responses to irradiated NOD islet cells but not irradiated NOD spleen cells were observed for both male and female NOD animals. Insulin, phogrin and phogrin-peptide 7 (aa 755-777) but not phogrin-peptide 2 (aa 640-659) or tetanus toxin peptide were recognized as antigens. Islet cell-reactive and phogrin peptide 7-specific CD4+ T-cell lines were generated from splenocytes of unprimed 4-week-old NOD females and shown to secrete Th1-type cytokines. The results show that the phogrin molecule is targeted early in the course of disease in NOD animals at a time when circulating autoantibodies are absent and insulitis is minimal.

AB - Phogrin (IA-2β), a major autoantigen in type 1 diabetes in man is recognized by peripheral T cells in the nonobese diabetic (NOD) mouse. CD4+ T-cell clones derived from immunized NOD animals elicit islet destruction in a disease transfer model. Spontaneous proliferative responses to the protein and derived peptide epitopes were detected in peripheral lymph node cells (LNC) of unprimed NOD mice but not BALB/c controls as early as 4 weeks of age at a time point when insulitis in NOD animals is minimal. Responses to irradiated NOD islet cells but not irradiated NOD spleen cells were observed for both male and female NOD animals. Insulin, phogrin and phogrin-peptide 7 (aa 755-777) but not phogrin-peptide 2 (aa 640-659) or tetanus toxin peptide were recognized as antigens. Islet cell-reactive and phogrin peptide 7-specific CD4+ T-cell lines were generated from splenocytes of unprimed 4-week-old NOD females and shown to secrete Th1-type cytokines. The results show that the phogrin molecule is targeted early in the course of disease in NOD animals at a time when circulating autoantibodies are absent and insulitis is minimal.

KW - Autoantigen

KW - Diabetes

KW - IA-2β

KW - NOD mouse

KW - T-cell response

UR - http://www.scopus.com/inward/record.url?scp=0036849453&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036849453&partnerID=8YFLogxK

U2 - 10.1006/jaut.2002.0611

DO - 10.1006/jaut.2002.0611

M3 - Article

C2 - 12419281

AN - SCOPUS:0036849453

VL - 19

SP - 111

EP - 116

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

IS - 3

ER -