Functional characterisation of two receptor interaction determinants in human thymic stromal lymphopoietin

Iva Marković; Therese Wolfrum; Andreas Wohlmann; Kritan Gautam; Karlheinz Friedrich

doi:10.1515/hsz-2021-0293

Functional characterisation of two receptor interaction determinants in human thymic stromal lymphopoietin

Biol Chem. 2021 Oct 26;403(2):243-249. doi: 10.1515/hsz-2021-0293. Print 2022 Jan 27.

Authors

Iva Marković¹, Therese Wolfrum¹, Andreas Wohlmann¹, Kritan Gautam¹, Karlheinz Friedrich¹

Affiliation

¹ Institute of Biochemistry II, University Hospital Jena, Nonnenplan 2-4, D-07743 Jena, Germany.

PMID: 34699696
DOI: 10.1515/hsz-2021-0293

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.

Keywords: TSLP; cellular surface display; cytokine receptor; thymic stromal lymphopoietin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cytokines* / chemistry
Humans
Interleukin-7 Receptor alpha Subunit
Protein Domains
Receptors, Cytokine* / genetics
Thymic Stromal Lymphopoietin

Substances

Cytokines
IL7R protein, human
Interleukin-7 Receptor alpha Subunit
Receptors, Cytokine
Thymic Stromal Lymphopoietin