title: [Functional properties of cooperative monoclonal antibodies against human tumor necrosis factor].
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.
authors.affiliation: Institute of Pediatrics, Obstetrics and Gynecology, Academy of Medical Sciences of Ukraine, Kiev.
authors.forename: M O
authors.initials: MO
authors.lastname: Vodianyk
authors.forename: V P
authors.initials: VP
authors.lastname: Chernyshov
authors.forename: M Ie
authors.initials: MIe
authors.lastname: Humeniuk
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D018604:Epitope Mapping / Q000379:methods; D000939:Epitopes / Q000032:analysis; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011487:Protein Conformation; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha
vernacular_title: Funktsional'ni vlastyvosti kooperatsiĭnykh monoklonal'nykh antytil proty faktora nekrozu pukhlyn liudyny.