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Antibody-Mediated Suppression of the Immune Response in vitro

IV. The Effect of Antibody Fragments^1,2,

From the Walter and Eliza Hall Institute of Medical Research, Post Office, Royal Melbourne Hospital, Victoria, 3050, Australia, and the MRC Transplantation Unit, Department of Pathology, University of Alberta, Edmonton, Canada

Abstract

The capacity of purified Fab' and F(ab')₂ pepsin antibody fragments to inhibit the immune response to polymerized flagellin in vitro was investigated. Marked differences between the activities of these fragments were found. Only high doses of univalent Fab' were suppressive, whereas much smaller amounts of divalent F(ab)'₂ were active. Preincubation experiments were performed to determine whether these fragments were capable of potentiating the induction of tolerance in vitro. Only F(ab)'₂ fragments facilitated the induction of antibody-mediated tolerance; Fab' fragments, regardless of dose, were inactive. These findings highlighted several important aspects of the mechanism of antibody-induced suppression. First, the difference in activity of Fab' and F(ab')₂, despite the same antigen-binding capacity and affinity, demonstrated the existence of at least two different mechanisms of antibody-induced immune suppression in vitro. Second, the importance of divalency for the induction of tolerance strongly supports the antigen cross-linking hypothesis of antibody-mediated tolerance as recently proposed by Diener and Feldmann. Third, the Fc part of the IgG molecule was not involved in the mechanism of antibody-mediated tolerance in vitro.

Footnotes

¹ This study was supported by grants from the National Health and Medical Research Council, Canberra, Australia, The Australian Research Grants Committee, and the United States Public Health Service Grant No. AI-O-3958 to Prof. G. J. V. Nossal.

² This is publication No. 1558 from the Walter and Eliza Hall Institute of Medical Research.

³ Supported by a National Health and Medical Research Council Postgraduate Fellowship.