Anne Hodgson Evans

US Patent:

20080153112, Jun 26, 2008

Filed:

May 20, 2004

Appl. No.:

10/557273

Inventors:

Teresa P. DiLorenzo - Bayside NY, US
Anne M. Evans - Chapel Hill NC, US
Donald F. Hunt - Charlottesville VA, US
Scott M. Lieberman - Bronx NY, US
Stanley G. Nathenson - Pelham Manor NY, US
Pere Santamaria - Calgary CA, US
Jeffrey Shabanowitz - Charlottesville VA, US

International Classification:

A61K 31/711
A61K 38/08
A61P 3/10
C07H 21/02
C07H 21/04
C07K 14/00
C07K 7/00
C12N 5/06
G01N 33/567

US Classification:

435 721, 435375, 514 15, 514 16, 514 44, 530324, 530326, 530327, 530328, 530350, 536 231, 536 245

Abstract:

The present invention is based on the identification of a predominant ligand of CD8+ T cells that are responsible eq for type diabetes. That ligand is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Several CD8+ T 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 CD8+ T cells in autoimmune diabetes. The invention thus provides oligopeptide and polypeptide compositions comprising YLKTN/A/I/L/V)FL, FLWSVFWLI, (T/A)YY/G/T)FLNFM, LR(LV)(F/L)(G/N)IDLL, KWCANPDWI, and SFCKSASIP. 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 CD8+ T cell that is cytotoxic to pancreatic islet β-cells from destroying a mammalian β-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.