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 language | English |
|---|---|
| Pages (from-to) | 853-859 |
| Number of pages | 7 |
| Journal | Journal of Immunology |
| Volume | 171 |
| Issue number | 2 |
| State | Published - Jul 15 2003 |
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ASJC Scopus subject areas
- Immunology
Cite this
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 journal › Article
}
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.
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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 -