The Journal of Immunology, Vol 154, Issue 12 6446-6452, Copyright © 1995 by American Association of Immunologists

ARTICLES

The natural human IgG anti-F(ab')2 antibody recognizes a conformational IgG1 hinge epitope

P Terness, I Kohl, G Hubener, R Battistutta, L Moroder, M Welschof, C Dufter, M Finger, C Hain and M Jung
Department of Transplantation Immunology, University of Heidelberg, Germany.

Natural IgG anti-F(ab')2 Abs are part of the physiologic immune repertoire and have important immunoregulatory functions. Although previous work suggested that some of these Abs recognize epitopes located in the constant region of the F(ab')2 molecule, an exact epitope mapping has not been performed. We found that the anti-F(ab')2 Ab binds strongly to F(ab')2 but only weakly to Fab fragments. Fab fragments are lacking the core and lower hinge region. In our experiments, we show that the IgG anti-F(ab')2 Ab binds strongly to a synthetic double chain peptide (225-237/225'-237') comprising the core and lower hinge region of the human IgG1 molecule. In contrast, it binds only weakly to the same peptide in monomeric form (225-237) or to a short double chain hinge peptide (225-232/225'-232'). The double chain peptides comprise a cyclic region between the two cystine bridges and an exocyclic region. Previous nuclear magnetic resonance analyses showed that the cyclic portion of the short double chain hinge peptide adopts the same conformation as that found in the intact IgG1 molecule. The dichroic properties of the short and long double chain hinge peptides indicate that they have identical conformations in their cyclic regions, but have different conformations in their exocyclic regions. The conformational differences in the exocyclic regions explain the binding of the Ab to the long double chain hinge peptide and the lack of binding to the short one. The circular dichroism spectrum of the monomeric hinge peptide, which is not recognized by the Ab, is consistent with the absence of an ordered peptide structure. These findings lead us to conclude that the IgG anti-F(ab')2 Ab recognizes a conformational IgG1 hinge epitope.

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