Peptides from common viral and bacterial pathogens can efficiently activate diabetogenic T-cells

Valeria A. Judkowski, Gina M. Allicotti, Nora E Sarvetnick, Clemencia Pinilla

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cross-reactivity between an autoantigen and unknown microbial epitopes has been proposed as a molecular mechanism involved in the development of insulin-dependent diabetes (type 1 diabetes). Type 1 diabetes is an autoimmune disease that occurs in humans and the nonobese diabetic (NOD) mouse. BDC2.5 is an islet-specific CD4+ T-cell clone derived from the NOD mouse whose natural target antigen is unknown. A biometrical analysis of screening data from BDC2.5 T-cells and a positional scanning synthetic combinatorial library (PS-SCL) was used to analyze and rank all peptides in public viral and bacterial protein databases and identify potential molecular mimic sequences with predicted reactivity. Selected sequences were synthesized and tested for stimulatory activity with BDC2.5 T-cells. Active peptides were identified, and some of them were also able to stimulate spontaneously activated T-cells derived from young, pre-diabetic NOD mice, indicating that the reactivity of the BDC2.5 T-cell is directed at numerous mouse peptides. Our results provide evidence for their possible role as T-cell ligands involved in the activation of diabetogenic T-cells.

Original languageEnglish (US)
Pages (from-to)2301-2309
Number of pages9
JournalDiabetes
Volume53
Issue number9
DOIs
StatePublished - Sep 1 2004
Externally publishedYes

Fingerprint

T-Lymphocytes
Peptides
Inbred NOD Mouse
Type 1 Diabetes Mellitus
Protein Databases
Bacterial Proteins
Autoantigens
Viral Proteins
Autoimmune Diseases
Epitopes
Clone Cells
Insulin
Ligands
Antigens

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Peptides from common viral and bacterial pathogens can efficiently activate diabetogenic T-cells. / Judkowski, Valeria A.; Allicotti, Gina M.; Sarvetnick, Nora E; Pinilla, Clemencia.

In: Diabetes, Vol. 53, No. 9, 01.09.2004, p. 2301-2309.

Research output: Contribution to journalArticle

Judkowski, Valeria A. ; Allicotti, Gina M. ; Sarvetnick, Nora E ; Pinilla, Clemencia. / Peptides from common viral and bacterial pathogens can efficiently activate diabetogenic T-cells. In: Diabetes. 2004 ; Vol. 53, No. 9. pp. 2301-2309.
@article{fb2fffdb225645c599aeea42baff31da,
title = "Peptides from common viral and bacterial pathogens can efficiently activate diabetogenic T-cells",
abstract = "Cross-reactivity between an autoantigen and unknown microbial epitopes has been proposed as a molecular mechanism involved in the development of insulin-dependent diabetes (type 1 diabetes). Type 1 diabetes is an autoimmune disease that occurs in humans and the nonobese diabetic (NOD) mouse. BDC2.5 is an islet-specific CD4+ T-cell clone derived from the NOD mouse whose natural target antigen is unknown. A biometrical analysis of screening data from BDC2.5 T-cells and a positional scanning synthetic combinatorial library (PS-SCL) was used to analyze and rank all peptides in public viral and bacterial protein databases and identify potential molecular mimic sequences with predicted reactivity. Selected sequences were synthesized and tested for stimulatory activity with BDC2.5 T-cells. Active peptides were identified, and some of them were also able to stimulate spontaneously activated T-cells derived from young, pre-diabetic NOD mice, indicating that the reactivity of the BDC2.5 T-cell is directed at numerous mouse peptides. Our results provide evidence for their possible role as T-cell ligands involved in the activation of diabetogenic T-cells.",
author = "Judkowski, {Valeria A.} and Allicotti, {Gina M.} and Sarvetnick, {Nora E} and Clemencia Pinilla",
year = "2004",
month = "9",
day = "1",
doi = "10.2337/diabetes.53.9.2301",
language = "English (US)",
volume = "53",
pages = "2301--2309",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "9",

}

TY - JOUR

T1 - Peptides from common viral and bacterial pathogens can efficiently activate diabetogenic T-cells

AU - Judkowski, Valeria A.

AU - Allicotti, Gina M.

AU - Sarvetnick, Nora E

AU - Pinilla, Clemencia

PY - 2004/9/1

Y1 - 2004/9/1

N2 - Cross-reactivity between an autoantigen and unknown microbial epitopes has been proposed as a molecular mechanism involved in the development of insulin-dependent diabetes (type 1 diabetes). Type 1 diabetes is an autoimmune disease that occurs in humans and the nonobese diabetic (NOD) mouse. BDC2.5 is an islet-specific CD4+ T-cell clone derived from the NOD mouse whose natural target antigen is unknown. A biometrical analysis of screening data from BDC2.5 T-cells and a positional scanning synthetic combinatorial library (PS-SCL) was used to analyze and rank all peptides in public viral and bacterial protein databases and identify potential molecular mimic sequences with predicted reactivity. Selected sequences were synthesized and tested for stimulatory activity with BDC2.5 T-cells. Active peptides were identified, and some of them were also able to stimulate spontaneously activated T-cells derived from young, pre-diabetic NOD mice, indicating that the reactivity of the BDC2.5 T-cell is directed at numerous mouse peptides. Our results provide evidence for their possible role as T-cell ligands involved in the activation of diabetogenic T-cells.

AB - Cross-reactivity between an autoantigen and unknown microbial epitopes has been proposed as a molecular mechanism involved in the development of insulin-dependent diabetes (type 1 diabetes). Type 1 diabetes is an autoimmune disease that occurs in humans and the nonobese diabetic (NOD) mouse. BDC2.5 is an islet-specific CD4+ T-cell clone derived from the NOD mouse whose natural target antigen is unknown. A biometrical analysis of screening data from BDC2.5 T-cells and a positional scanning synthetic combinatorial library (PS-SCL) was used to analyze and rank all peptides in public viral and bacterial protein databases and identify potential molecular mimic sequences with predicted reactivity. Selected sequences were synthesized and tested for stimulatory activity with BDC2.5 T-cells. Active peptides were identified, and some of them were also able to stimulate spontaneously activated T-cells derived from young, pre-diabetic NOD mice, indicating that the reactivity of the BDC2.5 T-cell is directed at numerous mouse peptides. Our results provide evidence for their possible role as T-cell ligands involved in the activation of diabetogenic T-cells.

UR - http://www.scopus.com/inward/record.url?scp=4344698785&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4344698785&partnerID=8YFLogxK

U2 - 10.2337/diabetes.53.9.2301

DO - 10.2337/diabetes.53.9.2301

M3 - Article

VL - 53

SP - 2301

EP - 2309

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 9

ER -