Johns Hopkins University

Leland Stanford Junior University

Dax Fu

Chengfeng Merriman

Hongjie Dai

Hao Wan

The present invention relates to the fields of immunology and diabetes. More specifically, the present invention provides methods and compositions directed to the use of antibodies to quantify cellular pancreatic zinc transporter 8. In certain embodiment, the present invention provides methods and compositions directed to the use of antibodies to screen for modulators of the pancreatic zinc transporter, ZnT8. In one embodiment, a method comprises the steps of (a) permeabilizing human beta cells present in a substrate; (b) contacting the cells with a test agent; and (c) measuring the amount of zinc transporter 8 (ZnT8) using at least one anti-ZnT8 antibody or antigen-binding fragment thereof.

Cell-based ZNT8 assay

The present invention relates to the fields of immunology and autoimmunity. More specifically, the present invention provides methods and compositions directed to the generation and use of antibodies to the pancreatic zinc transporter, ZnT8. The present invention also provides an isolated antibody or antigen-binding fragment thereof that specifically binds ZnT8 comprising a VH comprising one of the amino acid sequences set forth in SEQ ID NOS:2, 12, 22, 32, 42 and 52. In alternative embodiments an isolated antibody or antigen-binding fragment thereof that specifically binds ZnT8 comprises a VL comprising one of the amino acid sequences as set forth in SEQ ID NOS:7, 17, 27, 37, 47 and 57.

Antibodies to human ZnT8

Methods of detecting ZNT8 antibodies in serum are described. The methods include proteoliposomes comprising a transmembrane domain (TMD) and a cytosolic domain (CTD) of ZnT8 proteins exposed on the exterior of the proteoliposome; serum comprising antibodies targeting the ZnT8 proteins; and labelled captured autoantibodies that bind to ZnT8 antibodies.

Proteoliposome-based ZnT8 self-antigen for type 1 diabetes diagnosis

The present invention describes methods of identifying drugs for the treatment or prevention of diabetes by measuring the activity of the human zinc transporter ZnT8 and pharmaceutical compositions.

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Short Hills, NJ, United States of America

Dax Fu