This year, SYSU-CHINA developed a reversible safe switch for CAR T therapy based on the tet-inducible CMV promoter and U24 protein of Human Herpesvirus 6. Since it is the major part of our project, we conducted extensive research on U24 and obtained valuable results. Yet we believed we did not discover the full potential of this protein. By submitting to the registry, we aim to add a new tool to the toolbox of T cells functions regulation. We are confident that it will benefit teams in the future ambitious to conduct T cell- related project.
U24 is a small (87aa) tail-anchored protein (Sullivan and Coscoy, 2010) that can downregulate
TCR/CD3 complex from the cell surface by exclusion of CD3 from Rab11-containing recycling endosomes and thus inhibiting TCR complex
recycling back to the surface (Sullivan and Coscoy, 2008) . While it was demonstrated later
that U24 also downregulate transferrin (Sullivan and Coscoy, 2010) , its action is relatively
specific, without affecting the surface level of ICAM-1, MHC class I, ULBP1, ULBP2, CD4 and CD8
(Sullivan and Coscoy, 2008) . Since U24 does not colocalized with CD3, it is believed that the downregulation does not rely on
the interaction of U24 with CD3 but instead results from interaction of U24 and the endosomal recycling machinery
(Sullivan and Coscoy, 2010) . In addition, unlike proteins from other herpesviruses that
downregulate TCRs or B cell receptors (BCRs), U24 does not activate lymphocyte signaling pathways
(Sullivan and Coscoy, 2008) . Furthermore, it was demonstrated that U24 can impair T cell activation by antigen presenting
cells (Sullivan and Coscoy, 2008) .
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