Journal article
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
The Journal of immunology (1950), Vol.173(11), pp.6727-6734
12/01/2004
DOI: 10.4049/jimmunol.173.11.6727
PMID: 15557165
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 beta cell-reactive T cells cultured from islets of individual NOD mice. Even within age-matched groups, each individual mouse exhibited a unique distribution of beta 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 beta cell-specific autoimmune response.
Details
- Title: Subtitle
- 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
- Creators
- Scott M Lieberman - Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USAToshiyuki TakakiBingye HanPere SantamariaDavid V SerrezeTeresa P DiLorenzo
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.173(11), pp.6727-6734
- DOI
- 10.4049/jimmunol.173.11.6727
- PMID
- 15557165
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- DK64315 / NIDDK NIH HHS DK46266 / NIDDK NIH HHS CA13330 / NCI NIH HHS DK20541 / NIDDK NIH HHS DK52956 / NIDDK NIH HHS GM07288 / NIGMS NIH HHS DK51090 / NIDDK NIH HHS
- Language
- English
- Date published
- 12/01/2004
- Academic Unit
- Stead Family Department of Pediatrics; Rheumatology, Allergy, and Immunology
- Record Identifier
- 9984093333702771
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