Proteomic analysis in primary T cells reveals IL-7 alters T cell receptor thresholding via CYTIP/cytohesin/LFA-1 localisation and activation.
Queiroz, Rayner ML
Piper, Siân C
Low, Choon Pei
Ferguson, G John
Lilley, Kathryn S
Jackson, Antony P
Finch, Donna K
Portland Press Ltd.
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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
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.
CYTIP/cytohesin, IL7, LFA, Phosphoproteomics, SPPLAT, TCR
Biotechnology and Biological Sciences Research Council (BB/J021091/1)
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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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