Functional characterisation of two receptor interaction determinants in human thymic stromal lymphopoietin
Author:
Marković Iva1ORCID, Wolfrum Therese1, Wohlmann Andreas1, Gautam Kritan1, Friedrich Karlheinz1
Affiliation:
1. Institute of Biochemistry II, University Hospital Jena , Nonnenplan 2-4 , D-07743 Jena , Germany
Abstract
Abstract
Thymic stromal lymphopoietin (TSLP) is a pro-inflammatory cytokine with important pathological roles in Asthma bronchiale, malignant tumours and other diseases. The heterodimeric human TSLP receptor (hTSLPR) consists of the TSLP-binding subunit (TSLPRα) and the IL-7Rα-subunit. We studied the properties of hTSLP variants with mutations in their bipartite interaction interface towards IL-7Rα. One mutant (T46D/K101D) showed only mild impairment in receptor affinity but a massive reduction in biological activity. To facilitate the future development of hTSLP mutants with drug properties, we have devised a eukaryontic cytokine display assay with activity read-out and intrinsic genotype-phenotype coupling.
Publisher
Walter de Gruyter GmbH
Subject
Clinical Biochemistry,Molecular Biology,Biochemistry
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