Proteomic analysis in primary T cells reveals IL-7 alters T cell receptor thresholding via CYTIP/cytohesin/LFA-1 localisation and activation.
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Authors
Queiroz, Rayner ML
Piper, Siân C
Strickson, Sam
Briend, Emmanuel
Low, Choon Pei
Ferguson, G John
Lilley, Kathryn S
Jackson, Antony P
Finch, Donna K
Publication Date
2022-02-11Journal Title
Biochem J
ISSN
0264-6021
Publisher
Portland Press Ltd.
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Queiroz, R. M., Piper, S. C., Rees, J. S., Strickson, S., Briend, E., Low, C. P., Ferguson, G. J., et al. (2022). Proteomic analysis in primary T cells reveals IL-7 alters T cell receptor thresholding via CYTIP/cytohesin/LFA-1 localisation and activation.. Biochem J https://doi.org/10.1042/BCJ20210313
Abstract
The ability of the cellular immune system to discriminate self from foreign antigens depends on the appropriate calibration of the T cell receptor (TCR) signalling threshold. The lymphocyte homeostatic cytokine interleukin 7 (IL-7) is known to affect TCR thresholding, but the molecular mechanism is not fully elucidated. A better understanding of this process is highly relevant in the context of autoimmune disease therapy and cancer immunotherapy. We sought to characterise the early signalling events attributable to IL-7 priming; in particular, the altered phosphorylation of signal transduction proteins and their molecular localisation to the TCR. By integrating high-resolution proximity- phospho-proteomic and imaging approaches using primary T cells, rather than engineered cell lines or an in vitro expanded T cell population, we uncovered transduction events previously not linked to IL-7. We show that IL-7 leads to dephosphorylation of cytohesin interacting protein (CYTIP) at a hitherto undescribed phosphorylation site (pThr280) and alters the co-localisation of cytohesin-1 with the TCR and LFA-1 integrin. These results show that IL-7, acting via CYTIP and cytohesin-1, may impact TCR activation thresholds by enhancing the co-clustering of TCR and LFA-1 integrin.
Keywords
CYTIP/cytohesin, IL7, LFA, Phosphoproteomics, SPPLAT, TCR
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/J021091/1)
Identifiers
External DOI: https://doi.org/10.1042/BCJ20210313
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332866
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