Antigen discrimination by T cells relies on size-constrained microvillar contact.
Antigen discrimination by T cells relies on size-constrained microvillar contact.
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DOI：
10.1038/s41467-023-36855-9
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发表时间：
2023-03-23
影响因子：
16.6
通讯作者：
Klenerman, David
中科院分区：
文献类型：
--
作者：
Jenkins, Edward;Korbel, Markus;O'Brien-Ball, Caitlin;McColl, James;Chen, Kevin Y.;Kotowski, Mateusz;Humphrey, Jane;Lippert, Anna H.;Brouwer, Heather;Santos, Ana Mafalda;Lee, Steven F.;Davis, Simon J.;Klenerman, David
T细胞使用一种叫做“微绒毛”的手指状突起来询问它们的目标，但它们这样做的原因尚不清楚。为了形成接触，T细胞必须克服形成靶细胞糖萼的大分子的高电荷屏障层。在这里，观察到T细胞使用微绒毛突破模型糖calyx屏障，形成许多小的（<0.5 μm直径）接触，每个接触都由T细胞表达的小粘附蛋白CD2稳定，并排除包括CD45在内的大蛋白，从而允许敏感的抗原依赖性TCR信号传导。当糖萼缺失或微绒毛接触大小通过增强CD2表达而增加时，发生不再依赖抗原的强信号传导。我们的观察结果表明，在靶细胞糖萼和小粘附蛋白的相反作用的调节下，微绒毛的使用使T细胞具有影响歧视性受体信号传导的能力。T细胞可以利用微绒毛上的TCR与抗原呈递细胞上的多肽- mhc （pMHC）复合物相互作用。在这里，作者描述了T细胞如何使用微绒毛来询问pMHC复合物的重组膜，以及这是如何通过减少检测的糖蛋白/糖杯和增强检测的小粘附蛋白CD2之间的平衡来调节的。
T cells use finger-like protrusions called ‘microvilli’ to interrogate their targets, but why they do so is unknown. To form contacts, T cells must overcome the highly charged, barrier-like layer of large molecules forming a target cell’s glycocalyx. Here, T cells are observed to use microvilli to breach a model glycocalyx barrier, forming numerous small (<0.5 μm diameter) contacts each of which is stabilized by the small adhesive protein CD2 expressed by the T cell, and excludes large proteins including CD45, allowing sensitive, antigen dependent TCR signaling. In the absence of the glycocalyx or when microvillar contact-size is increased by enhancing CD2 expression, strong signaling occurs that is no longer antigen dependent. Our observations suggest that, modulated by the opposing effects of the target cell glycocalyx and small adhesive proteins, the use of microvilli equips T cells with the ability to effect discriminatory receptor signaling. T cells can use TCR on microvilli to interact with peptide-MHC (pMHC) complexes on antigen presenting cells. Here the authors characterise how T cells use microvilli to interrogate reconstituted membranes for pMHC complexes and how this is regulated by a balance between glycoproteins/glycocalyces that reduce detection, and the small adhesion protein CD2, which enhances detection.
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影响因子：
30.5
作者：
Chang VT;Fernandes RA;Ganzinger KA;Lee SF;Siebold C;McColl J;Jönsson P;Palayret M;Harlos K;Coles CH;Jones EY;Lui Y;Huang E;Gilbert RJC;Klenerman D;Aricescu AR;Davis SJ
通讯作者：
Davis SJ
影响因子：
5.7
作者：
BODIAN, DL;JONES, EY;DAVIS, SJ
通讯作者：
DAVIS, SJ
影响因子：
4.4
作者：
Dumortier, H;van Mierlo, GJD;Melief, CJM
通讯作者：
Melief, CJM
影响因子：
30.8
作者：
Frangieh CJ;Melms JC;Thakore PI;Geiger-Schuller KR;Ho P;Luoma AM;Cleary B;Jerby-Arnon L;Malu S;Cuoco MS;Zhao M;Ager CR;Rogava M;Hovey L;Rotem A;Bernatchez C;Wucherpfennig KW;Johnson BE;Rozenblatt-Rosen O;Schadendorf D;Regev A;Izar B
通讯作者：
Izar B
影响因子：
30.5
作者：
Demetriou P;Abu-Shah E;Valvo S;McCuaig S;Mayya V;Kvalvaag A;Starkey T;Korobchevskaya K;Lee LYW;Friedrich M;Mann E;Kutuzov MA;Morotti M;Wietek N;Rada H;Yusuf S;Afrose J;Siokis A;Oxford IBD Cohort Investigators;Meyer-Hermann M;Ahmed AA;Depoil D;Dustin ML
通讯作者：
Dustin ML