CD5-mediated inhibition of TCR signaling proceeds normally in the absence of SHP-1

Dong,Baoxia; Somani,Ally-Khan; Love,Paul  E.; Zheng,Xuan; Chen,Xiequn; Zhang,Jinyi

doi:10.3892/ijmm.2016.2592

CD5-mediated inhibition of TCR signaling proceeds normally in the absence of SHP-1

Authors:
- Baoxia Dong
- Ally-Khan Somani
- Paul E. Love
- Xuan Zheng
- Xiequn Chen
- Jinyi Zhang
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Affiliations: Department of Haematology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Lunenfeld‑Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada, The Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
Published online on: May 17, 2016 https://doi.org/10.3892/ijmm.2016.2592
Pages: 45-56
Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The CD5 transmembrane glycoprotein functions as a co-receptor in the signaling pathway linking T-cell antigen receptor (TCR) engagement to activation and differentiation. Although CD5 effects on TCR signaling have been shown to be primarily inhibitory, the underlying mechanisms remain unclear. In view of recent data revealing the ability of CD5 to associate with the SHP-1 tyrosine phosphatase, a protein that also downregulates TCR signaling, we examined the role of SHP-1 in modulating CD5 function using thymocytes from SHP-1‑deficient viable motheaten (mev) mice. The results revealed the association of SHP-1 with CD5 to be markedly increased following TCR stimulation and indicated that this interaction was enhanced by and was dependent on CD5 tyrosine phosphorylation. However, there was no difference of the tyrosine phosphorylation status of CD5 between resting and TCR-stimulated cells in SHP-1‑deficient compared to wild-type thymocytes. Lack of SHP-1 activity did not affect the levels of CD5 surface expression, CD5 co-immunoprecipitable tyrosine phosphatase activity and intracellular calcium increase following co-crosslinking of the TCR and CD5. Similarly, an analysis of T‑cell thymocyte populations in mev mice expressing an H-Y transgene as well as a construct mediating T‑cell restricted CD5 overexpression, revealed that the reduction in the positive selection conferred by CD5 overexpression was unaffected by SHP-1 deficiency. CD5 is not a SHP-1 substrate and SHP-1 is not required for and possibly not involved in the CD5-mediated modulation of TCR signaling.

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