Daga, Sunil, Moyse, Harry, Briggs, David, Lowe, David Philip, Evans, Neil D., Jones, James, Buchli, Rico, McMurtrey, Curtis, Mulder, Arend, Hildebrand, William, Claas, Frans, Higgins, Rob, Mitchell, Daniel A. and Zehnder, Daniel (2018) Direct quantitative measurement of the kinetics of HLA-specific antibody interactions with isolated HLA proteins. Human Immunology, 79 (2). pp. 122-128. doi:10.1016/j.humimm.2017.10.012 ISSN 0198-8859.
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Abstract
HLA specific antibodies vary in their pathogenicity and this is likely to be the net effect of constant chain usage, quantity, specificity, and affinity. Here we have measured the affinity of human monoclonal antibodies for a range of HLA proteins. Purified antibodies and ligands allowed dynamic interactions to be measured directly by surface plasmon resonance. Physiochemical differences between pairs of ligands were quantified using electrostatic mismatch and hydrophobic mismatch scores.
All antibodies were characterized by fast on-rates and slow off rates but with a wide range of association rates (kon, 3.63-24.25 × 10(5) per mol per second) and dissociation rates (koff, 0.99-10.93 × 10(-3) per second). Dissociation constants (KD) ranged from 5.9 × 10(-10) M to 3.0 × 10(-8) M. SN320G6 has approximately a twenty-fold greater affinity for HLA A2 compared with SN607D8, but has a similar affinity for HLA-A2 and B57. In contrast, SN607D8 has greater than a twofold greater affinity for HLA-A2 compared with A68. Similarly, WK1D12 has about a threefold greater affinity for HLA-B27 compared with B7. The higher affinity interactions correlate with the specificity of stimulating antigen. This is the first study to directly measure the binding kinetics and affinity constants for human alloantibodies against HLA.
| Item Type: | Journal Article |
|---|---|
| Subjects: | Q Science > QR Microbiology > QR180 Immunology |
| Divisions: | Faculty of Science, Engineering and Medicine > Engineering > Engineering Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
| SWORD Depositor: | Library Publications Router |
| Library of Congress Subject Headings (LCSH): | HLA histocompatibility antigens, Transplantation of organs, tissues, etc., Monoclonal antibodies, Antigenic determinants, Chemical kinetics, Chemical affinity, Surface plasmon resonance |
| Journal or Publication Title: | Human Immunology |
| Publisher: | Elsevier Science BV |
| ISSN: | 0198-8859 |
| Official Date: | February 2018 |
| Dates: | Date Event February 2018 Published 31 October 2017 Available 26 October 2017 Accepted |
| Volume: | 79 |
| Number: | 2 |
| Page Range: | pp. 122-128 |
| DOI: | 10.1016/j.humimm.2017.10.012 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Re-use Statement: | ** From PubMed via Jisc Publications Router. ** History: received 13-06-2017; revised 11-10-2017; accepted 26-10-2017. |
| Access rights to Published version: | Restricted or Subscription Access |
| Date of first compliant deposit: | 15 February 2018 |
| Date of first compliant Open Access: | 31 October 2018 |
| RIOXX Funder/Project Grant: | Project/Grant ID RIOXX Funder Name Funder ID UNSPECIFIED National Institute for Health Research (Great Britain). West Midlands (South) Comprehensive Local Research Network (NIHR-CLRN) UNSPECIFIED Coventry Renal Research Fund University Hospitals Coventry and Warwickshire NHS Trust |
| URI: | https://wrap.warwick.ac.uk/94714/ |
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