Human clonal CD8 autoreactivity to an IGRP islet epitope shared between mice and men.
Type 1 diabetes (T1D) is a multifactorial disease characterized by the infiltration and subsequent destruction of the pancreatic insulin-producing beta cells by autoreactive T cells. CD8(+) T cells play an essential role in this beta 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), IGRP(265-273,) 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.
Unger
W W J
WW
Department of Immunohematology and Blood Transfusion, LUMC, E3-Q, P.O. Box 9600, 2300 RC Leiden, the Netherlands. w.w.j.unger@lumc.nl
Pinkse
G G M
GG
Mulder-van der Kracht
S
S
van der Slik
A R
AR
Kester
M G D
MG
Ossendorp
F
F
Drijfhout
J W
JW
Serreze
D V
DV
Roep
B O
BO
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D005952:Glucose-6-Phosphatase / Q000276:immunology*; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D051379:Mice; D011506:Proteins / Q000276:immunology*
D001324:Autoantigens; D016827:CD8 Antigens; D000939:Epitopes; D011506:Proteins; D005952:Glucose-6-Phosphatase; C492194:G6PC2 protein, human; C117983:G6pc2 protein, mouse