E-cadherin in developing murine T cells controls spindle alignment and progression through β-selection

Author:

Charnley Mirren12ORCID,Allam Amr H.12,Newton Lucas M.34ORCID,Humbert Patrick O.3456ORCID,Russell Sarah M.127ORCID

Affiliation:

1. Optical Sciences Centre, School of Science, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia.

2. Immune Signalling Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.

3. Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.

4. Research Centre for Molecular Cancer Prevention, La Trobe University, Melbourne, Victoria 3086, Australia.

5. Department of Biochemistry and Pharmacology, University of Melbourne, Melbourne, Victoria 3010, Australia.

6. Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria 3010, Australia.

7. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria 3010, Australia.

Abstract

A critical stage of T cell development is β-selection; at this stage, the T cell receptor β (TCRβ) chain is generated, and the developing T cell starts to acquire antigenic specificity. Progression through β-selection is assisted by low-affinity interactions between the nascent TCRβ chain and peptide presented on stromal major histocompatibility complex and cues provided by the niche. In this study, we identify a cue within the developing T cell niche that is critical for T cell development. E-cadherin mediates cell-cell interactions and influences cell fate in many developmental systems. In developing T cells, E-cadherin contributed to the formation of an immunological synapse and the alignment of the mitotic spindle with the polarity axis during division, which facilitated subsequent T cell development. Collectively, these data suggest that E-cadherin facilitates interactions with the thymic niche to coordinate the β-selection stage of T cell development.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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