The Open UniversitySkip to content
 

A novel vascular targeting strategy for brain-derived endothelial cells using a TCR mimic antibody

Bhattacharya, Raktima; Xu, Yan; Rahman, Md. Ashequr; Couraud, Pierre-Olivier; Romero, Ignacio A.; Weksler, Babette B.; Weidanz, Jon A. and Bickel, Ulrich (2010). A novel vascular targeting strategy for brain-derived endothelial cells using a TCR mimic antibody. Journal of Cellular Physiology, 225(3) pp. 664–672.

Full text available as:
Full text not publicly available
Due to copyright restrictions, this file is not available for public download
Click here to request a copy from the OU Author.
DOI (Digital Object Identifier) Link: http://dx.doi.org/10.1002/jcp.22256
Google Scholar: Look up in Google Scholar

Abstract

Organ-specific vascular targeting, for example, to the blood–brain barrier, requires the identification of unique molecular addresses on a subset of endothelial cells. The present study describes a crucial step towards tapping the exquisite specificity of the peptide/HLA class I system for this goal. We utilized a novel T-cell receptor (TCR) mimic antibody of high affinity and specificity, which is restricted by HLA-A2 and has been generated to recognize a peptide epitope derived from p68 RNA helicase (YLLPAIVHI). The parent protein is highly expressed by brain endothelial cells. Flow cytometry and confocal imaging showed that the antibody binds to HLA-A2-positive human brain-derived endothelial cells, both immortalized hCMEC/D3 cells and primary cells. The TCR mimic antibody undergoes internalization into vesicles, where significant colocalization occurs with the early endosomal marker EEA-1, but barely with caveolin-1. To our knowledge internalization of neither MHC class I protein nor TCR mimics by brain endothelial cells has been previously observed. Knock down of p68 protein expression by siRNA reduced the presentation of YLLPAIVHI-peptide/HLA-A2 complexes on the cell membrane by half as measured by flow cytometry 48?h later. We also found that brain endothelial cells isolated from HLA-A2 transgenic mouse strains express the A2 transgene, and brain endothelial cells of one of these strains also present YLLPAIVHI-peptide/HLA-A2, making these mouse strains suitable models for studying TCR mimic antibodies in vivo. In conclusion, these data strongly support the notion that TCR mimic antibodies could be a new class of therapeutic targeting agents in a wide variety of diseases

Item Type: Journal Article
Copyright Holders: 2010 Wiley-Liss, Inc.
ISSN: 0021-9541
Academic Unit/Department: Science > Life, Health and Chemical Sciences
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 23837
Depositing User: Astrid Peterkin
Date Deposited: 19 Oct 2010 10:29
Last Modified: 07 Mar 2014 23:07
URI: http://oro.open.ac.uk/id/eprint/23837
Share this page:

Actions (login may be required)

View Item
Report issue / request change

Policies | Disclaimer

© The Open University   + 44 (0)870 333 4340   general-enquiries@open.ac.uk