PMID: 15220192Jun 29, 2004Paper

HLA-DQ-regulated T-cell responses to islet cell autoantigens insulin and GAD65

Diabetes
Timothy I M TreeBart O Roep

Abstract

HLA-DQ is strongly associated with genetic predisposition to type 1 diabetes. It is assumed that HLA-DQ molecules exert their effects on the disease via the presentation of peptides from islet autoantigens to CD4(+) T-cells, but little information regarding HLA-DQ-restricted, islet antigen-specific, autoreactive T-cells is available. To investigate the role of HLA-DQ in the immune response to islet autoantigens, we measured T-cell proliferation to insulin and GAD65 in the presence and absence of monoclonal antibodies that block HLA-DQ-mediated antigen presentation in recent-onset type 1 diabetic patients and their siblings. Positive proliferative T-cell responses to GAD65 were observed in 60% of type 1 diabetic patients and 52% of siblings. This proliferation was significantly reduced in the presence of anti-DQ antibody, demonstrating the presence of primed, effector HLA-DQ-restricted T-cell responses to GAD65. Positive proliferative responses to insulin were observed in 25% of type 1 diabetic patients and 10% of siblings. However, blocking HLA-DQ-restricted T-cell responses led to a significant increase in proliferation to insulin, implying the presence of primed suppressive HLA-DQ-restricted T-cell responses to insulin. These...Continue Reading

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Citations

Aug 22, 2007·Cell Biochemistry and Biophysics·Todd Brusko, Mark Atkinson
Dec 21, 2011·The Journal of Biological Chemistry·Menno van LummelFrits Koning
Jun 3, 2005·Current Opinion in Clinical Nutrition and Metabolic Care·Anne BouloumiéRudi Busse
Oct 2, 2007·Current Opinion in Gastroenterology·Iordanes Karagiannides, Charalabos Pothoulakis
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Apr 29, 2005·Diabetes/metabolism Research and Reviews
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Apr 28, 2006·International Immunology·Anthony QuinnEli Sercarz
Feb 2, 2021·Immunology and Cell Biology·Stuart I Mannering, Pushpak Bhattacharjee

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