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Human Clonal CD8 Autoreactivity to an IGRP Islet Epitope Shared between Mice and Men


Address for correspondence: Wendy W.J. Unger, Ph.D., Department of Immunohematology and Blood Transfusion, LUMC, E3-Q, P.O. Box 9600, 2300 RC Leiden, the Netherlands. Voice: +31-71-2563800; fax: +31-71-5265267.


Abstract: Type 1 diabetes (T1D) is a multifactorial disease characterized by the infiltration and subsequent destruction of the pancreatic insulin-producing β cells by autoreactive T cells. CD8+ T cells play an essential role in this β cell destruction. However, little is known about the target antigens of CD8+ T cells in human T1D patients. The aim of this study was to assess whether an epitope derived from the islet-specific glucose-6-phosphatase catalytic subunit–related protein (IGRP), IGRP265-273, which has recently been identified as a target in non-obese diabetic (NOD) mice and is fully homologous to the human epitope, is a target of human diabetogenic CD8+ T cells. We isolated a human CD8 T cell clone against this epitope, which confirms that this IGRP epitope is shared across species.

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