UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Arginine residues are important in determining the binding of human monoclonal antiphospholipid antibodies to clinically relevant antigens
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Giles I, Lambrianides N, Pattni N, Faulkes D, Latchman D, Chen P, Pierangeli S, Isenberg D, Rahman A
  • Publication date:
    01/08/2006
  • Pagination:
    1729, 1736
  • Journal:
    The Journal of Immunology
  • Volume:
    177
  • Issue:
    3
  • Print ISSN:
    0022-1767
  • Keywords:
    14, 96, 97, A, ALL, AND, Antibodies, Antibody, ANTIGEN, Antigens, Antiphospholipid Syndrome, Arginine, BINDING, BOTH, cell, CELLS, Chain, COMBINATION, DEVELOPED, EFFECT, ELISA, EXPRESSION, Human, I, Igg, IN, in vitro, IN-VITRO, MAJOR, Mutation, MUTATIONS, NUMBER, OF, Ovary, Ovum, phospholipid, PHOSPHOLIPIDS, Plasmids, POSITION, PROTEIN, Proteins, REPLACEMENT, Result, SEQUENCE, SEQUENCES, Syndrome, THE, TO, Transfection
Abstract
In the antiphospholipid syndrome (APS), antiphospholipid Abs (aPL) bind to anionic phospholipids (PL) and various associated proteins, especially beta(2)-glycoprotein I (beta2GPI) and prothrombin. In the present study, we show that altering specific Arg residues in the H chain of a human pathogenic beta2GPI-dependent aPL, IS4, has major effects on its ability to bind these clinically important Ags. We expressed whole human IgG in vitro by stable transfection of Chinese hamster ovary cells with expression plasmids containing different V(H) and V(L) sequences. V(H) sequences were derived from IS4 by altering the number of Arg residues in CDR3. V(L) sequences were those of IS4, B3 (anti-nucleosome Ab), and UK4 (beta2GPI-independent aPL). Binding of the expressed H/L chain combinations to a range of anionic, neutral, and zwitterionic PL, as well as prothrombin, beta2GPI, dsDNA, and chicken OVA, was determined by ELISA. Of four Arg residues in IS4VH CDR3 substituted to Ser, two at positions 100 and 100g, reduced binding to all Ags, while two at positions 96 and 97 reduced binding to beta2GPI but increased or decreased binding to different PL. Eleven of 14 H/L chain combinations displayed weak binding to OVA with Arg to Ser replacements of all four Arg residues enhancing binding to this Ag. Only one H/L chain combination bound neutral PL and none bound dsDNA; hence, these effects are particularly relevant to Ags important in antiphospholipid syndrome. We hypothesize that these four Arg residues have developed as a result of somatic mutations driven by an Ag containing both PL and beta2GPI
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
Author
Inflammation
Author
ICH - Directors Office
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by