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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2001; 47(3): 73-79


Functional properties ofcooperative monoclonal antibodies against human tumor necrosis factor

M.A. Vodyanik, V.P. Chernyshov, M.E. Gumenyuk

    Institute of Pediatrics, Obstetrics and Gynecology, Academy of MedicalSciences of Ukraine, Kiev


Abstract

The panel of 23 newly produced monoclonal antibodies (mAbs) against human tumor necrosis factor (TNF) was examined for enhanced or cooperative TNF binding. Epitopic mapping revealed a preferential mAb generation against two epitopes designed as A1 and C1. Both A1 and C1 mAbs have neutralizing activity and display remarkable property to bind TNF synergistically comprising a pair of cooperative mAbs. C1 epitope resides within the TNF receptor-binding site (RBS) and responsible for generation of competitive neutralizing mAbs that block TNF activity by direct RBS masking. RBS-distal A1 epitope represents allosteric neutralizing mAbs that block TNF activity by conformational RBS changes. Combination of A1 and C1 mAbs resulted in synergistic TNF neutralization through complementary effect of competitive and allosteric TNF blocking mechanisms. Generation of cooperative Abs may have significance to achieve the most efficient neutralization of protein antigens with an intolerable functional activity in vivo.

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