Editing of an immunodominant epitope of glutamate decarboxylase by HLA-DM

John D. Lich, Jennifer A. Jayne, Delu Zhou, John F. Elliott, Janice Blum

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

HLA-DM stabilizes peptide-receptive class II αβ dimers and facilitates the capture of high affinity peptides, thus influencing the peptide repertoire presented by class II molecules. Variations in DM levels may therefore have a profound effect on the antigenic focus of T cell-mediated immune responses. Specifically, DM expression may influence susceptibility and resistance to autoimmune diseases. In this study the role of DM in HLA-DR4-restricted presentation of an insulin-dependent diabetes mellitus autoantigen, glutamate decarboxylase (GAD), was tested. Presentation of immunodominant GAD epitope 273-285 was regulated by endogenous DM levels in human B lymphoblasts. T cell responses to exogenous GAD as well as an endogenous cytoplasmic form of this Ag were significantly diminished with increasing cellular expression of DM. Epitope editing by DM was observed only using Ag and not small synthetic peptides, suggesting that this process occurred within endosomes. Results with cytoplasmic GAD also indicated that peptides from this compartment intersect class II proteins in endocytic vesicles where DM editing was facilitated. Changes in DM levels within APC may therefore influence the presentation of autoantigens and the development of autoimmune disorders such as type I diabetes.

Original languageEnglish
Pages (from-to)853-859
Number of pages7
JournalJournal of Immunology
Volume171
Issue number2
StatePublished - Jul 15 2003

Fingerprint

Immunodominant Epitopes
Glutamate Decarboxylase
Peptides
Autoantigens
Type 1 Diabetes Mellitus
Epitopes
HLA-DR4 Antigen
T-Lymphocytes
Transport Vesicles
Endosomes
Autoimmune Diseases
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Lich, J. D., Jayne, J. A., Zhou, D., Elliott, J. F., & Blum, J. (2003). Editing of an immunodominant epitope of glutamate decarboxylase by HLA-DM. Journal of Immunology, 171(2), 853-859.

Editing of an immunodominant epitope of glutamate decarboxylase by HLA-DM. / Lich, John D.; Jayne, Jennifer A.; Zhou, Delu; Elliott, John F.; Blum, Janice.

In: Journal of Immunology, Vol. 171, No. 2, 15.07.2003, p. 853-859.

Research output: Contribution to journalArticle

Lich, JD, Jayne, JA, Zhou, D, Elliott, JF & Blum, J 2003, 'Editing of an immunodominant epitope of glutamate decarboxylase by HLA-DM', Journal of Immunology, vol. 171, no. 2, pp. 853-859.
Lich JD, Jayne JA, Zhou D, Elliott JF, Blum J. Editing of an immunodominant epitope of glutamate decarboxylase by HLA-DM. Journal of Immunology. 2003 Jul 15;171(2):853-859.
Lich, John D. ; Jayne, Jennifer A. ; Zhou, Delu ; Elliott, John F. ; Blum, Janice. / Editing of an immunodominant epitope of glutamate decarboxylase by HLA-DM. In: Journal of Immunology. 2003 ; Vol. 171, No. 2. pp. 853-859.
@article{589c8b1295bb49c5bc2f28b504552e78,
title = "Editing of an immunodominant epitope of glutamate decarboxylase by HLA-DM",
abstract = "HLA-DM stabilizes peptide-receptive class II αβ dimers and facilitates the capture of high affinity peptides, thus influencing the peptide repertoire presented by class II molecules. Variations in DM levels may therefore have a profound effect on the antigenic focus of T cell-mediated immune responses. Specifically, DM expression may influence susceptibility and resistance to autoimmune diseases. In this study the role of DM in HLA-DR4-restricted presentation of an insulin-dependent diabetes mellitus autoantigen, glutamate decarboxylase (GAD), was tested. Presentation of immunodominant GAD epitope 273-285 was regulated by endogenous DM levels in human B lymphoblasts. T cell responses to exogenous GAD as well as an endogenous cytoplasmic form of this Ag were significantly diminished with increasing cellular expression of DM. Epitope editing by DM was observed only using Ag and not small synthetic peptides, suggesting that this process occurred within endosomes. Results with cytoplasmic GAD also indicated that peptides from this compartment intersect class II proteins in endocytic vesicles where DM editing was facilitated. Changes in DM levels within APC may therefore influence the presentation of autoantigens and the development of autoimmune disorders such as type I diabetes.",
author = "Lich, {John D.} and Jayne, {Jennifer A.} and Delu Zhou and Elliott, {John F.} and Janice Blum",
year = "2003",
month = "7",
day = "15",
language = "English",
volume = "171",
pages = "853--859",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - Editing of an immunodominant epitope of glutamate decarboxylase by HLA-DM

AU - Lich, John D.

AU - Jayne, Jennifer A.

AU - Zhou, Delu

AU - Elliott, John F.

AU - Blum, Janice

PY - 2003/7/15

Y1 - 2003/7/15

N2 - HLA-DM stabilizes peptide-receptive class II αβ dimers and facilitates the capture of high affinity peptides, thus influencing the peptide repertoire presented by class II molecules. Variations in DM levels may therefore have a profound effect on the antigenic focus of T cell-mediated immune responses. Specifically, DM expression may influence susceptibility and resistance to autoimmune diseases. In this study the role of DM in HLA-DR4-restricted presentation of an insulin-dependent diabetes mellitus autoantigen, glutamate decarboxylase (GAD), was tested. Presentation of immunodominant GAD epitope 273-285 was regulated by endogenous DM levels in human B lymphoblasts. T cell responses to exogenous GAD as well as an endogenous cytoplasmic form of this Ag were significantly diminished with increasing cellular expression of DM. Epitope editing by DM was observed only using Ag and not small synthetic peptides, suggesting that this process occurred within endosomes. Results with cytoplasmic GAD also indicated that peptides from this compartment intersect class II proteins in endocytic vesicles where DM editing was facilitated. Changes in DM levels within APC may therefore influence the presentation of autoantigens and the development of autoimmune disorders such as type I diabetes.

AB - HLA-DM stabilizes peptide-receptive class II αβ dimers and facilitates the capture of high affinity peptides, thus influencing the peptide repertoire presented by class II molecules. Variations in DM levels may therefore have a profound effect on the antigenic focus of T cell-mediated immune responses. Specifically, DM expression may influence susceptibility and resistance to autoimmune diseases. In this study the role of DM in HLA-DR4-restricted presentation of an insulin-dependent diabetes mellitus autoantigen, glutamate decarboxylase (GAD), was tested. Presentation of immunodominant GAD epitope 273-285 was regulated by endogenous DM levels in human B lymphoblasts. T cell responses to exogenous GAD as well as an endogenous cytoplasmic form of this Ag were significantly diminished with increasing cellular expression of DM. Epitope editing by DM was observed only using Ag and not small synthetic peptides, suggesting that this process occurred within endosomes. Results with cytoplasmic GAD also indicated that peptides from this compartment intersect class II proteins in endocytic vesicles where DM editing was facilitated. Changes in DM levels within APC may therefore influence the presentation of autoantigens and the development of autoimmune disorders such as type I diabetes.

UR - http://www.scopus.com/inward/record.url?scp=0038445901&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038445901&partnerID=8YFLogxK

M3 - Article

C2 - 12847254

AN - SCOPUS:0038445901

VL - 171

SP - 853

EP - 859

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -