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- Title
Characterization of neutralizing antibodies reacting with the 213-224 amino-acid segment of human galectin-9.
- Authors
Lhuillier, Claire; Barjon, Clément; Baloche, Valentin; Niki, Toshiro; Gelin, Aurore; Mustapha, Rami; Claër, Laetitia; Hoos, Sylviane; Chiba, Yoichi; Ueno, Masaki; Hirashima, Mitsuomi; Wei, Ming; Morales, Olivier; Raynal, Bertrand; Delhem, Nadira; Dellis, Olivier; Busson, Pierre
- Abstract
Extra-cellular galectin-9 (gal-9) is an immuno-modulatory protein with predominant immunosuppressive effects. Inappropriate production of gal-9 has been reported in several human malignancies and viral diseases like nasopharyngeal, pancreatic and renal carcinomas, metastatic melanomas and chronic active viral hepatitis. Therefore therapeutic antibodies neutralizing extra-cellular gal-9 are expected to contribute to immune restoration in these pathological conditions. Two novel monoclonal antibodies targeting gal-9 –Gal-Nab 1 and 2—have been produced and characterized in this study. We report a protective effect of Gal-Nab1 and Gal-Nab2 on the apoptotic cell death induced by gal-9 in primary T cells. In addition, they inhibit late phenotypic changes observed in peripheral T cells that survive gal-9-induced apoptosis. Gal-Nab1 and Gal-Nab2 bind nearly identical, overlapping linear epitopes contained in the 213–224 amino-acid segments of gal-9. Nevertheless, they have some distinct functional characteristics suggesting that their three-dimensional epitopes are distinct. These differences are best demonstrated when gal-9 is applied on Jurkat cells where Gal-Nab1 is less efficient than Gal-Nab2 in the prevention of apoptotic cell death. In addition, Gal-Nab1 stimulates non-lethal phosphatidylserine translocation at the plasma membrane and calcium mobilization triggered by gal-9 in these cells. Both Gal-Nab1 and 2 cross-react with murine gal-9. They bind its natural as well as its recombinant form. This cross-species recognition will be an advantage for their assessment in pre-clinical tumor models.
- Subjects
IMMUNOGLOBULINS; VIRUS diseases; AMINO acids; GALECTINS; IMMUNOSUPPRESSIVE agents
- Publication
PLoS ONE, 2018, Vol 13, Issue 9, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0202512