Two monoclonal antibodies to precisely the same epitope of type II collagen select non-crossreactive phage clones by phage display: Implications for autoimmunity and molecular mimicry

Xu, Yuekang, Ramsland, Paul A., Davies, Janet M., Scealy, Marita, Nandakumar, Kutty Selva, Holmdahl, Rikard and Rowley, Merrill J. (2004) Two monoclonal antibodies to precisely the same epitope of type II collagen select non-crossreactive phage clones by phage display: Implications for autoimmunity and molecular mimicry. Molecular Immunology, 41 4: 411-419. doi:10.1016/j.molimm.2004.03.025


Author Xu, Yuekang
Ramsland, Paul A.
Davies, Janet M.
Scealy, Marita
Nandakumar, Kutty Selva
Holmdahl, Rikard
Rowley, Merrill J.
Title Two monoclonal antibodies to precisely the same epitope of type II collagen select non-crossreactive phage clones by phage display: Implications for autoimmunity and molecular mimicry
Journal name Molecular Immunology   Check publisher's open access policy
ISSN 0161-5890
Publication date 2004-06-01
Sub-type Article (original research)
DOI 10.1016/j.molimm.2004.03.025
Open Access Status
Volume 41
Issue 4
Start page 411
End page 419
Total pages 9
Place of publication Oxford ; New York
Publisher Pergamon Press
Language eng
Subject 110703 Autoimmunity
110705 Humoural Immunology and Immunochemistry
Abstract Two monoclonal antibodies (mAb) CB268 and CII-C1 to type II collagen (CII) react with precisely the same conformational epitope constituted by the residues ARGLT on the three chains of the CII triple helix. The antibodies share structural similarity, with most differences in the complementarity determining region 3 of the heavy chain (HCDR3). The fine reactivity of these mAbs was investigated by screening two nonameric phage-displayed random peptide libraries. For each mAb, there were phage clones (phagotopes) that reacted strongly by ELISA only with the selecting mAb, and inhibited binding to CII only for that mAb, not the alternate mAb. Nonetheless, a synthetic peptide RRLPFGSQM corresponding to an insert from a highly reactive CII-C1-selected phagotope, which was unreactive (and non-inhibitory) with CB268, inhibited the reactivity of CB268 with CII. Most phage-displayed peptides contained a motif in the first part of the molecule that consisted of two basic residues adjacent to at least one hydrophobic residue (e.g. RRL or LRR), but the second portion of the peptides differed for the two mAbs. We predict that conserved CDR sequences interact with the basic–basic-hydrophobic motif, whereas non-conserved amino acids in the binding sites (especially HCDR3) interact with unique peptide sequences and limit cross-reactivity. The observation that two mAbs can react identically with a single epitope on one antigen (CII), but show no cross-reactivity when tested against a second (phagotope) indicates that microorganisms could exhibit mimics capable of initiating autoimmunity without this being evident from conventional assays.
Keyword Collagen-induced arthritis
Autoimmune disease
Phage display
C1 epitope
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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