Evidences that syngeneic alpha-type anti-idiotypic antibodies may non-competitively inhibit idiotype/oligomeric antigen interactions by affecting idiotype avidity

Angelo Corti, Elena Barbanti, Fabrizio Marcucci, Giovanni Cassani

Research output: Contribution to journalArticle

Abstract

The effects of syngeneic anti-Id antibodies on the multivalent interaction between human TNF-alpha, a homotrimeric Ag, and an anti-TNF mAb (mAb178) have been studied. Eight anti-mAb178 Ig secreting hybridoma, able to inhibit TNF binding in a competitive or non-competitive mode, have been generated. Two representative clones (mAb21G3 and mAb29F1) were selected for studying the inhibition mechanism of TNF-mAb178 interaction. Idiotype-paratope topography studies indicated that mAb21G3 (IgG2a) and mAb29F1 (IgG1) bind two sterically distinct idiotopes on mAb178 (IgG1) V regions. In particular, mAb2lG3 was found to bind an idiotope located within (or spatially close to) the Ag combining site suggesting that competitive inhibition of TNF binding to mAb178 by mAb11G3 occurs through paratope blockade. On the other hand, mAb29F1 recognizes an idiotope located outside the paratope, being able to bind mAb178 even in the presence of saturating amounts of TNF. mAb178-TNF molar ratio in complexes, at stoichiometric equivalence, was unchanged in the presence of a large excess of mAb29F1, suggesting that the functional bivalency of mAb178 was not impaired by this anti-Id antibody. However, bivalent mAb29F1 was able to partially inhibit the binding of bivalent mAb178 to oligomeric TNF in liquid-phase as well as in solid-phase assays, whereas no inhibition was observed with monovalent mAb29F1-F(ab) or mAb178-F(ab). This suggests that inhibition is based on a decrease of the avidity of bivalent mAb178 and not on allosteric effects on antigen binding sites. The effect of mAb29F1 on mAb178 arm flexibility and paratope orientation is discussed. In conclusion, the results indicate that anti-Id antibodies may inhibit Ag-antibody multivalent interactions by paratope blockade or by affecting the antibody avidity.

Original languageEnglish
Pages (from-to)1123-1131
Number of pages9
JournalMolecular Immunology
Volume30
Issue number12
DOIs
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

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