Identification of novel IGRP epitopes targeted in type 1 diabetes patients.
CD8(+) T cells play an important role in the development of type 1 diabetes (T1D) in NOD mice and humans. IGRP (islet-specific glucose-6-phosphatase catalytic subunit-related protein) has emerged in recent years as a major antigen in NOD mice. Therefore, we aimed to determine if IGRP is an antigen in T1D patients and to identify the HLA-A2-restricted IGRP epitopes targeted. Using IFN-gamma ELISPOT assay, we tested PBMC from recent-onset pediatric T1D patients and healthy controls for reactivity to four IGRP peptides directly ex vivo. Importantly, 65% of patients and 0% of controls were positive for at least one IGRP peptide. Two of these have not been reported previously. These data provide evidence that IGRP is a CD8(+) T cell antigen in humans, contributing to the understanding of the underlying disease process as well as to future directions for diagnosis and monitoring disease progression in T1D patients.
Jarchum
Irene
I
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Nichol
Lynn
L
Trucco
Massimo
M
Santamaria
Pere
P
DiLorenzo
Teresa P
TP
D000293:Adolescent; D000328:Adult; D001324:Autoantigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005952:Glucose-6-Phosphatase / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D010455:Peptides / Q000276:immunology / Q000378:metabolism
D001324:Autoantigens; D000939:Epitopes; D015789:HLA-A2 Antigen; D010455:Peptides; D007371:Interferon-gamma; D005952:Glucose-6-Phosphatase; C492194:G6PC2 protein, human