Identification of the β cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes

Scott M. Lieberman, Anne M. Evans, Bingye Han, Toshiyuki Takaki, Yuliya Vinnitskaya, Jennifer A. Caldwell, David V. Serreze, Jeffrey Shabanowitz, Donald F. Hunt, Stanley G. Nathenson, Pere Santamaria, Teresa P. DiLorenzo

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309 Scopus citations

Abstract

Type 1 diabetes is an autoimmune disease in which autoreactive T cells attack and destroy the insulin-producing pancreatic β cells. CD8+ T cells are essential for this β cell destruction, yet their specific antigenic targets are largely unknown. Here, we reveal that the autoantigen targeted by a prevalent population of pathogenic CD8+ T cells in nonobese diabetic mice is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Through tetramer technology, IGRP-reactive T cells are readily detected in islets and peripheral blood directly ex vivo. The human IGRP gene maps to a diabetes susceptibility locus, suggesting that IGRP also may be an antigen for pathogenic T cells in human type 1 diabetes and, thus, a new, potential target for diagnostic and therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)8384-8388
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number14
DOIs
StatePublished - Jul 8 2003

ASJC Scopus subject areas

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    Lieberman, S. M., Evans, A. M., Han, B., Takaki, T., Vinnitskaya, Y., Caldwell, J. A., Serreze, D. V., Shabanowitz, J., Hunt, D. F., Nathenson, S. G., Santamaria, P., & DiLorenzo, T. P. (2003). Identification of the β cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes. Proceedings of the National Academy of Sciences of the United States of America, 100(14), 8384-8388. https://doi.org/10.1073/pnas.0932778100