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Title

Rheumatoid factor autoantibody-binding site: a molecular analysis using monoclonal antibodies with dual anti-TNP and anti-IgG activities

Authors
Reininger, Luc
Spertini, F.
Shibata, T.
Jaton, J. C.
Published in European Journal of Immunology. 1989, vol. 19, no. 11, p. 2123-2130
Abstract Two out of five murine IgG3 anti-trinitrophenyl (TNP) monoclonal antibodies (mAb) obtained either by immunization with TNP-keyhole limpet hemocyanin (KLH) (CB1, CB5, CB6 and 4H10) or with dinitrophenyl-lipopolysaccharide (9A6), exhibited anti-IgG rheumatoid factor (RF) activity (CB6 and 4H10). The anti-IgG activity of these two anti-TNP RF was specifically inhibited by murine IgG as well as by the hapten TNP. In order to identify the structural basis for the anti-IgG activity, the nucleotide sequences encoding the VH and VL regions were determined. By comparing the V regions of the non-RF and RF anti-TNP mAb, it was found that one anti-TNP RF antibody, CB6, shares virtually identical VL and VH regions with two anti-TNP antibodies, CB1 and CB5, but markedly differs from these in the D region. Furthermore, the light chain framework region 2 (FR2) and FR3 of non-RF mAb, CB1, CB5 and 9A6, have amino acid sequences almost identical to those claimed for anti-IgG1 RF activity (Shlomchik et al., J. Exp. Med. 1986. 164: 407). Our findings suggest, at least in the case of CB6 mAb, the involvement of CDR, but not light chain FR residues, in IgG binding.
Keywords Amino Acid SequenceAnimalsAntibodies, Monoclonal/immunologyAutoantibodies/genetics/ immunologyBase SequenceBinding Sites, AntibodyImmunoglobulin Heavy Chains/physiologyImmunoglobulin Light Chains/physiologyImmunoglobulin Variable Region/ genetics/physiologyMiceMice, Inbred StrainsMolecular Sequence DataRNA, Messenger/geneticsRheumatoid Factor/genetics/ immunologyTrinitrobenzenes/immunology
Identifiers
PMID: 2513210
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REININGER, Luc et al. Rheumatoid factor autoantibody-binding site: a molecular analysis using monoclonal antibodies with dual anti-TNP and anti-IgG activities. In: European Journal of Immunology, 1989, vol. 19, n° 11, p. 2123-2130. doi: 10.1002/eji.1830191123 https://archive-ouverte.unige.ch/unige:10968

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Deposited on : 2010-08-26

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