Albert Einstein College of Medicine

University of Virginia Patent Foundation

University Technologies International, Inc.

The Jackson Laboratory

Scott M Lieberman

Teresa P DiLorenzo

Donald F Hunt

Jeffrey Shabanowitz

David V Serreze

Anne M Evans

Stanley G Nathenson

Pere Santamaria

The present invention is based on the identification of a predominant ligand of CD8T cells that are responsible for type 1 diabetes. That ligand is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Several CD8T cell-binding peptides from IGRP are identified, including the peptide comprising amino acids 206-214 of the IGRP sequence, which has high avidity to the most prevalent T cell receptor of pathogenic CD8T cells in autoimmune diabetes. The invention thus provides oligopeptide and polypeptide compositions comprising YLKTN(A/I/L/V)FL (SEQ ID NO:3), FLWSVFWLI (SEQ ID NO:4), (T/A)YY(G/T)FLNFM (SEQ ID NO:5), LR(L/V)(F/L)(G/N)IDLL (SEQ ID NO:6), KWCANPDWI (SEQ ID NO:7), and SFCKSASIP (SEQ ID NO:8). Also provided are oligopeptide compositions 8-10 amino acids in length and completely homologous with a mammalian IGRP, where the oligopeptide is capable of binding a human MHC class I molecule. Additionally, various methods of treating a mammal using the above compositions are provided, where the mammal is at risk for or has type 1 diabetes. Also provided are methods of preventing a CD8T cell that is cytotoxic to pancreatic islet &#x3b2;-cells from destroying a mammalian &#x3b2;-cell, where the methods also use the above compositions. Further provided are methods for determining whether a mammal is at risk for or has type 1 diabetes, where the methods use the above compositions.

Antigens targeted by prevalent pathogennic T cells in type 1 diabetes and uses thereof

Provided are oligopeptide antigens to AI4-like T cells, and mouse proteins comprising those antigens. The oligopeptide antigens comprise the amino acid sequence XX(I/D/F/L)ENY(I/L)(E/W/Y)(L/M) or VMLENYTHL. Additionally provided are methods for treating a mammal having or at risk for type 1 diabetes using these antigens, or compounds which reduce or eliminate expression of these antigens. Kits comprising these antigens, and methods for determining whether a mammal is at risk for or has type 1 diabetes are also provided.

Antigens targeted by pathogenic AI4 T cells in type 1 diabetes and uses thereof

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Scott M Lieberman