Individual nonobese diabetic mice exhibit unique patterns of CD8 + T cell reactivity to three islet antigens, including the newly identified widely expressed dystrophia myotonica kinase

Scott M. Lieberman, Toshiyuki Takaki, Bingye Han, Pere Santamaria, David V. Serreze, Teresa P. DiLorenzo

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Spontaneous autoimmune diabetes development in NOD mice requires both CD8+ and CD4+ T cells. Three pathogenic CD8+ T cell populations (represented by the G9C8, 8.3, and AI4 clones) have been described. Although the Ags for G9C8 and 8.3 are known to be insulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein, respectively, only mimotope peptides had previously been identified for AI4. In this study, we used peptide/MHC tetramers to detect and quantify these three pathogenic populations among β cell-reactive T cells cultured from islets of individual NOD mice. Even within age-matched groups, each individual mouse exhibited a unique distribution of β cell-reactive CD8+ T cells, both in terms of the number of tetramer-staining populations and the relative proportion of each population in the islet infiltrate. Thus, the inflammatory process in each individual follows its own distinctive course. Screening of a combinatorial peptide library in positional scanning format led to the identification of a peptide derived from dystrophia myotonica kinase (DMK) that is recognized by AI4-like T cells. Importantly, the antigenic peptide is naturally processed and presented by DMK-transfected cells. DMK is a widely expressed protein that is nonetheless the target of a β cell-specific autoimmune response.

Original languageEnglish (US)
Pages (from-to)6727-6734
Number of pages8
JournalJournal of Immunology
Volume173
Issue number11
DOIs
Publication statusPublished - Dec 1 2004

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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