The protective antibodies induced by a novel epitope of human TNF-alpha could suppress the development of collagen-induced arthritis.

PloS One
Jie DongGuang Yang

Abstract

Tumor necrosis factor alpha (TNF-alpha) is a major inflammatory mediator that exhibits actions leading to tissue destruction and hampering recovery from damage. At present, two antibodies against human TNF-alpha (hTNF-alpha) are available, which are widely used for the clinic treatment of certain inflammatory diseases. This work was undertaken to identify a novel functional epitope of hTNF-alpha. We performed screening peptide library against anti-hTNF-alpha antibodies, ELISA and competitive ELISA to obtain the epitope of hTNF-alpha. The key residues of the epitope were identified by means of combinatorial alanine scanning and site-specific mutagenesis. The N terminus (80-91 aa) of hTNF-alpha proved to be a novel epitope (YG1). The two amino acids of YG1, proline and valine, were identified as the key residues, which were important for hTNF-alpha biological function. Furthermore, the function of the epitope was addressed on an animal model of collagen-induced arthritis (CIA). CIA could be suppressed in an animal model by prevaccination with the derivative peptides of YG1. The antibodies of YG1 could also inhibit the cytotoxicity of hTNF-alpha. These results demonstrate that YG1 is a novel epitope associated with the biological ...Continue Reading

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Citations

Nov 20, 2013·Arthritis Research & Therapy·Daniela ImpellizzeriSalvatore Cuzzocrea
Oct 6, 2012·Biological & Pharmaceutical Bulletin·Renata GrespanRoberto Kenji Nakamura Cuman
Apr 3, 2012·International Immunopharmacology·Mansheng LuoJimin Gao
Sep 2, 2011·The Journal of Pharmacology and Experimental Therapeutics·Daniela ImpellizzeriSalvatore Cuzzocrea

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
phage display
phage
peptide
electrophoresis

Software Mentioned

DNAMAN

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