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

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.

journal_name

Eur J Immunol

authors

Reininger L,Spertini F,Shibata T,Jaton JC,Izui S

doi

10.1002/eji.1830191123

subject

Has Abstract

pub_date

1989-11-01 00:00:00

pages

2123-30

issue

11

eissn

0014-2980

issn

1521-4141

journal_volume

19

pub_type

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