Skip Navigation



PEDS Advance Access published online on October 29, 2008
Protein Engineering Design and Selection, doi:10.1093/protein/gzn058
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
22/3/159    most recent
gzn058v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Lloyd, C.
Right arrow Articles by Vaughan, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lloyd, C.
Right arrow Articles by Vaughan, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Modelling the human immune response: performance of a 1011 human antibody repertoire against a broad panel of therapeutically relevant antigens

C. Lloyd1, D. Lowe, B. Edwards, F. Welsh, T. Dilks, C. Hardman and T. Vaughan

MedImmune, Milstein Building, Granta Park, Cambridge CB21 6GH, UK

1 To whom correspondence should be addressed. lloydc{at}medimmune.com

A large 1.29 x 1011 antibody fragment library, based upon variable (V) genes isolated from human B-cells from 160 donors has been constructed and its performance measured against a panel of 28 different clinically relevant antigens. Over 5000 different target-specific antibodies were isolated to the 28 antigens with 3340 identified as modulating the biological function (e.g. antagonism, agonism) of the target antigen. This represents an average of ~120 different functionally active antibodies per target. Analysis of a sample of >800 antibodies from the unselected library indicates V gene usage is representative of the human immune system with no strong bias towards any particular VH–VL pairing. Germline diversity is broad with 45/49 functional VH germlines and 28/30 V{lambda} and 30/35 V{kappa} light-chain germlines represented in the sample. The number of functional VH germlines and V{kappa} light-chain germlines present is increased to 48/49 and 31/35, respectively, when selected V gene usage is included in the analysis. However, following selection on the antigen panel, VH1–V{lambda}1 germline family pairings are preferentially enriched and represent a remarkable 25% of the antigen-specific selected repertoire.

Keywords: antibody/human/library/phage display/scFv

Received September 15, 2008; revised September 15, 2008; accepted October 4, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.