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Euro Biotechnology 2016
November 07-09, 2016
Volume 6, Issue 7(Suppl) J Biotechnol Biomater
ISSN: 2155-952X JBTBM, an open access journal
conferenceseries .com
November 07-09, 2016 Alicante, Spain
12th Euro Biotechnology Congress
Marie Hlavnickova et al., J Biotechnol Biomater 2016, 6:7(Suppl)
Inhibitory binders derived fromABD-domain scaffold targeting human IL-17RA receptor as a non-
immunoglobulin alternative for modulation of Th17-mediated pro-inflammatory axis
Marie Hlavnickova1, Milan Kuchar1, Radim Osicka2, Lucie Mareckova 1, Hana Petrokova1, Jiri Cerny1 and Petr Maly1
1Institute of Biotechnology CAS, v.v.i., Czech Republic
2Institute of Microbiology CAS, v.v.i., Czech Republic
Interleukin 17 (IL-17) and its cognate receptor (IL-17RA) play a crucial role inTh17 cells-mediated pro-inflammatory pathway
and pathogenesis of several autoimmune disorders including psoriasis. Psoriasis is a chronic inflammatory skin disease with
prevalence up to 3% worldwide, it is characterized by hyperplasia of the epidermis, infiltration of leukocytes into both dermis
and epidermis and dilation and growth of blood vessels. IL-17 is mainly produced by Th-17 helper cells and via binding to
its receptor, mediates IL-17-driven cell signaling in keratinocytes. This work was aimed to generate novel protein binders of
IL-17RA that will prevent from binding of IL-17A cytokine to this receptor expressed on the surface of keratinocytes. To this
goal, we used a high-complex combinatorial library derived from scaffold of albumin-binding domain (ABD) of streptococcal
protein G and ribosome display selection, to yield a collection of ABD-derived high-affinity ligands of human IL-17RA called
ARS binders. From 67 analysed ABD variants, 7 different sequence families were identified. Representatives of these groups
competed with human IL-17A for binding to recombinant IL-17RA receptor as well as with IL-17RA-IgG chimera as tested
in ELISA. Five ARS variants bind to IL-17RA-expressing THP-1 and Raji cells, as tested by flow cytometry. The four variants
exhibited high-affinity binding in nanomolar range to human keratinocyte HaCAT cells, as measured using Ligand Tracer
Green Line system. Thus, we identified several ARS inhibitory variants with a blocking potential that will be further tested for
their immunomodulatory function.
Biography
Marie Hlavnickova is a PhD candidate at the 1st Faculty of Medicine, Charles University in Prague, Czech Republic. She is a Member of the Laboratory of Ligand
Engineering at the Institute of Biotechnology CAS, v.v.i., Czech Republic. Her research topic is focused on the development of inhibitory protein binders derived
from scaffold of albumin-binding domain and suppressing function of cytokine receptors modulating IL-23/Th17 pro-inflammatory axis.