Bhattacharya, Raktima; Xu, Yan; Rahman, Md. Ashequr; Couraud, Pierre-Olivier; Romero, Ignacio A.; Weksler, Babette B.; Weidanz, Jon A. and Bickel, Ulrich
(2010).
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| DOI (Digital Object Identifier) Link: | http://dx.doi.org/doi:10.1002/jcp.22256 |
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| 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 |
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| Copyright Holders: | 2010 Wiley-Liss, Inc. |
| ISSN: | 0021-9541 |
| Academic Unit/Department: | Science > Life, Health and Chemical Sciences |
| Item ID: | 23837 |
| Depositing User: | Astrid Peterkin |
| Date Deposited: | 19 Oct 2010 10:29 |
| Last Modified: | 02 Dec 2012 05:21 |
| URI: | http://oro.open.ac.uk/id/eprint/23837 |
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