Direct Regulation of the T Cell Antigen Receptor's Activity by Cholesterol
Pathan-Chhatbar, Salma1,2,3,4; Drechsler, Carina1,2,3,4; Richter, Kirsten5; Morath, Anna1,2,3,4; Wu, Wei6; OuYang, Bo6; Xu, Chenqi6,7; Schamel, Wolfgang W.1,2,3,4
AbstractBiological membranes consist of hundreds of different lipids that together with the embedded transmembrane (TM) proteins organize themselves into small nanodomains. In addition to this function of lipids, TM regions of proteins bind to lipids in a very specific manner, but the function of these TM region-lipid interactions is mostly unknown. In this review, we focus on the role of plasma membrane cholesterol, which directly binds to the alpha beta T cell antigen receptor (TCR), and has at least two opposing functions in alpha beta TCR activation. On the one hand, cholesterol binding to the TM domain of the TCR beta subunit keeps the TCR in an inactive, non-signaling conformation by stabilizing this conformation. This assures that the alpha beta T cell remains quiescent in the absence of antigenic peptide-MHC (the TCR's ligand) and decreases the sensitivity of the T cell toward stimulation. On the other hand, cholesterol binding to TCR beta leads to an increased formation of TCR nanoclusters, increasing the avidity of the TCRs toward the antigen, thus increasing the sensitivity of the alpha beta T cell. In mouse models, pharmacological increase of the cholesterol concentration in T cells caused an increase in TCR clustering, and thereby enhanced anti-tumor responses. In contrast, the gamma delta TCR does not bind to cholesterol and might be regulated in a different manner. The goal of this review is to put these seemingly controversial findings on the impact of cholesterol on the alpha beta TCR into perspective.
Keywordcholesterol lipid TCR signaling T cell nanocluster allostery
Indexed BySCIE
WOS Research AreaCell Biology ; Developmental Biology
WOS SubjectCell Biology ; Developmental Biology
WOS IDWOS:000610956100001
Original Document TypeReview
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Document Type期刊论文
Affiliation1.Univ Freiburg, Ctr Biol Signalling Studies, Freiburg, Germany;
2.Univ Freiburg, Ctr Integrat Biol Signalling Studies, Freiburg, Germany;
3.Univ Freiburg, Dept Immunol, Fac Biol, Freiburg, Germany;
4.Univ Freiburg, Ctr Chron Immunodeficiency CCI, Freiburg, Germany;
5.Roche Innovat Ctr Basel, Immunol Infect Dis & Ophthalmol Dis Translat Area, Basel, Switzerland;
6.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, State Key Lab Mol Biol, Shanghai, Peoples R China;
7.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
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Pathan-Chhatbar, Salma,Drechsler, Carina,Richter, Kirsten,et al. Direct Regulation of the T Cell Antigen Receptor's Activity by Cholesterol[J]. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,2021,8.
APA Pathan-Chhatbar, Salma.,Drechsler, Carina.,Richter, Kirsten.,Morath, Anna.,Wu, Wei.,...&Schamel, Wolfgang W..(2021).Direct Regulation of the T Cell Antigen Receptor's Activity by Cholesterol.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,8.
MLA Pathan-Chhatbar, Salma,et al."Direct Regulation of the T Cell Antigen Receptor's Activity by Cholesterol".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 8(2021).
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