The University of Southampton
University of Southampton Institutional Repository

The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20

Record type: Article

We have previously defined a panel of fully human CD20 mAb. Most of these were unexpectedly efficient in their ability to recruit C1q to the surface of CD20-positive cells and mediate tumor lysis via activation of the classical pathway of complement. This complement-dependent cytotoxicity (CDC) potency appeared to relate to the unusually slow off-rate of these human Abs. However, we now present epitope-mapping data, which indicates that all human mAb bind a novel region of CD20 that may influence CDC potency. Epitope mapping, using both mutagenesis studies and overlapping 15-mer peptides of the extracellular loops of CD20, defined the amino acids required for binding by an extensive panel of mouse and human mAb. Binding by rituximab and mouse CD20 mAb, had an absolute requirement for alanine and proline at positions 170 and 172, respectively, within the large extracellular loop of CD20. Surprisingly, however, all of the human CD20 mAb recognize a completely novel epitope located N-terminally of this motif, also including the small extracellular loop of CD20. Thus, although off-rate may influence biological activity of mAb, another critical factor for determining CDC potency by CD20 mAb appears to be the region of the target molecule they recognize. We conclude that recognition of the novel epitope cooperates with slow off-rate in determining the activity of CD20 Ab in activation of complement and induction of tumor cell lysis.

Full text not available from this repository.

Citation

Teeling, Jessica L., Mackus, Wendy J.M., Wiegman, Luus J.J.M., van den Brakel, Jeroen H.N., Beers, Stephen A., French, Ruth R., van Meerten, Tom, Ebeling, Saskia, Vink, Tom, Slootstra, Jerry W., Parren, Paul W.H.I., Glennie, Martin J. and van den Winkel, Jan G.J. (2006) The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20 Journal of Immunology, 177, (1), pp. 362-371.

More information

Published date: 1 July 2006

Identifiers

Local EPrints ID: 56216
URI: http://eprints.soton.ac.uk/id/eprint/56216
ISSN: 0022-1767
PURE UUID: 66e03bd1-3cf0-404c-ac0b-6c76274f3af4

Catalogue record

Date deposited: 08 Aug 2008
Last modified: 17 Jul 2017 14:31

Export record

Contributors

Author: Wendy J.M. Mackus
Author: Luus J.J.M. Wiegman
Author: Jeroen H.N. van den Brakel
Author: Ruth R. French
Author: Tom van Meerten
Author: Saskia Ebeling
Author: Tom Vink
Author: Jerry W. Slootstra
Author: Paul W.H.I. Parren
Author: Jan G.J. van den Winkel

University divisions


Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×