Research Papers: Immunology:
The kinesin motor protein Kif7 is required for Tcell development and normal MHC expression on thymic epithelial cells TEC in the thymus
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Ching-In Lau1,*, Alessandro Barbarulo1,*, Anisha Solanki1, José Ignacio Saldaña1,2 and Tessa Crompton1
1 Immunobiology Section, UCL Great Ormond Street Institute of Child Health, London, UK
2 School of Health, Sport and Bioscience, University of East London, London, UK
* These authors have contributed equally to this work
Correspondence to:
Tessa Crompton, email:
Keywords: Kif7, T-cell development, thymus, thymic epithelial cell, sonic hedgehog, Immunology and Microbiology Section, Immune response, Immunity
Received: December 10, 2016 Accepted: January 21, 2017 Published: February 09, 2017
Abstract
Kif7 is a ciliary kinesin motor protein that regulates mammalian Hedgehog pathway activation through influencing structure of the primary cilium. Here we show that Kif7 is required for normal T-cell development, despite the fact that T-cells lack primary cilia. Analysis of Kif7-deficient thymus showed that Kif7-deficiency increases the early CD44+CD25+CD4-CD8- thymocyte progenitor population but reduces differentiation to CD4+CD8+ double positive (DP) cell. At the transition from DP to mature T-cell, Kif7-deficiency selectively delayed maturation to the CD8 lineage. Expression of CD5, which correlates with TCR signal strength, was reduced on DP and mature CD4 and CD8 cells, as a result of thymocyte-intrinsic Kif7-deficiency, and Kif7-deficient T-cells from radiation chimeras activated less efficiently when stimulated with anti-CD3 and anti-CD28 in vitro. Kif7-deficient thymocytes showed higher expression of the Hedgehog target gene Ptch1 than WT, but were less sensitive to treatment with recombinant Shh, and Kif7-deficient T-cell development was refractory to neutralisation of endogenous Hh proteins, indicating that Kif7-deficient thymocytes were unable to interpret changes in the Hedgehog signal. In addition, Kif7-deficiency reduced cell-surface MHCII expression on thymic epithelial cells.