Identification of an epitope of tumor necrosis factor (TNF)-receptor type 1 (p55) recognized by a TNF-α-antagonist monoclonal antibody

A. Corti, L. Bagnasco, G. Cassani

Research output: Contribution to journalArticle

Abstract

The relationships between epitope topography and agonistic/antagonistic effects of anti-TNF receptor type 1 (TNF-R1) antibodies on TNF-α cytotoxic activity have been studied. To this purpose various monoclonal antibodies (mAbs) against the soluble form of TNF-R1 (sTNF-R1) have been generated and characterized. Epitope topography studies identified at least four distinct epitopes located outside (4E10) or within (or close to) the TNF-α binding site of urinary sTNF-R1 (7H3, 4C1, 9B11). mAbs 7H3 and 4C1 were able to neutralize the inhibition of human TNF-α cytotoxicity on L-M cells by sTNF- R1, while 4E10 was unable. Moreover, 7H3 and 4C1 were able to antagonize the TNF-α cytotoxicity on human U937 cells, while they were uneffective on mouse L-M cells, suggesting that these antibodies recognize, in a species-specific mode, also the membrane form of the human receptor. No agonistic effects were observed when these antibodies were used in the absence of TNF-α. Epitope topography studies carried out using overlapping decapeptides covering most of the sTNF-R1 sequence showed that residues 143-148 of the fourth cysteine- rich domain of the receptor (FFLREN) contain antigenic determinants recognized by the antagonist antibody 7H3. These results suggest that at least part of residues 143-148 of sTNF-R1 are surface exposed on the soluble as well as on the membrane forms of TNF-R1 and are accessible to TNF-α antagonists.

Original languageEnglish
Pages (from-to)183-190
Number of pages8
JournalLymphokine and Cytokine Research
Volume13
Issue number3
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Immunology
  • Hematology

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