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|Title:||Binding of TCR multimers and a TCR-like antibody with distinct fine-specificities is dependent on the surface density of HLA complexes||Authors:||Low, Jianrong L.
Gehring, Adam J.
Kranz, David M.
Grotenbreg, Gijsbert M.
Yau, Yin Hoe
Shochat, Susana Geifman
Ho, Zi Zong
|Keywords:||DRNTU::Science::Biological sciences||Issue Date:||2012||Source:||Low, J. L., Naidoo, A., Yeo, G., Gehring, A. J., Ho, Z. Z., Yau, Y. H., et al. (2012). Binding of TCR Multimers and a TCR-Like Antibody with Distinct Fine-Specificities Is Dependent on the Surface Density of HLA Complexes. PLoS ONE, 7(12), e51397.||Series/Report no.:||PLoS ONE||Abstract:||Class I Major Histocompatibility Complex (MHC) molecules evolved to sample degraded protein fragments from the interior of the cell, and to display them at the surface for immune surveillance by CD8+ T cells. The ability of these lymphocytes to identify immunogenic peptide-MHC (pMHC) products on, for example, infected hepatocytes, and to subsequently eliminate those cells, is crucial for the control of hepatitis B virus (HBV). Various protein scaffolds have been designed to recapitulate the specific recognition of presented antigens with the aim to be exploited both diagnostically (e.g. to visualize cells exposed to infectious agents or cellular transformation) and therapeutically (e.g. for the delivery of drugs to compromised cells). In line with this, we report the construction of a soluble tetrameric form of an αβ T cell receptor (TCR) specific for the HBV epitope Env183–191 restricted by HLA-A*02:01, and compare its avidity and fine-specificity with a TCR-like monoclonal antibody generated against the same HLA target. A flow cytometry-based assay with streptavidin-coated beads loaded with Env183–191/HLA-A*02:01 complexes at high surface density, enabled us to probe the specific interaction of these molecules with their cognate pMHC. We demonstrate that the TCR tetramer has similar avidity for the pMHC as the antibody, but they differ in their fine-specificity, with only the TCR tetramer being capable of binding both natural variants of the Env183–191 epitope found in HBV genotypes A/C/D (187Arg) and genotype B (187Lys). Collectively, the results highlight the promiscuity of our soluble TCR, which could be an advantageous feature when targeting cells infected with a mutation-prone virus, but that binding of the soluble oligomeric TCR relies considerably on the surface density of the presented antigen.||URI:||https://hdl.handle.net/10356/98967
|ISSN:||1932-6203||DOI:||10.1371/journal.pone.0051397||Rights:||© 2012 The Authors. This paper was published in PLoS ONE and is made available as an electronic reprint (preprint) with permission of The Authors. The paper can be found at the following official DOI: [http://dx.doi.org/10.1371/journal.pone.0051397]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Journal Articles|
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