# A centrally positioned cluster of multiple centrioles in antigen-presenting cells fosters T cell activation

**Authors:** Isabel Stötzel, Ann-Kathrin Weier, Apurba Sarkar, Subhendu Som, Luisa Bach, Peter Konopka, Eliška Miková, Shaunak Ghosh, Jan Böthling, Mirka Homrich, Laura Schaedel, Uli Kazmaier, Konstantinos Symeonidis, Stefan Ebner, Philip Weidner, Zeinab Abdullah, Felix Meissner, Stefan Uderhardt, Miroslav Hons, Dirk Baumjohann, Raja Paul, Heiko Rieger, Eva Kiermaier

PMC · DOI: 10.1038/s41467-026-68286-7 · 2026-01-13

## TL;DR

This study shows that extra centrioles in antigen-presenting cells help activate T cells by forming active microtubule centers.

## Contribution

The study reveals how centriole amplification in antigen-presenting cells influences T cell activation through centrosome dynamics.

## Key findings

- Dendritic cells amplify centrioles during immune activation.
- Extra centrioles form active microtubule organizing centers near the cell center.
- Disrupting centriole numbers or positioning impairs T cell activation.

## Abstract

Cellular polarization plays a crucial role in regulating immunological processes and is often associated with reorientation of the centrosome. During immune synapse formation, centrosome repositioning in lymphocytes assists in T cell activation. While a single centrosome, consisting of two centrioles, is present in T cells, antigen-presenting cells such as dendritic cells amplify centrioles during maturation and immune activation. How centriole amplification in antigen-presenting cells affects immune synapse formation and T cell activation is unclear. In this study, we combine experimental data with mathematical and computational modelling to provide evidence that extra centrioles in dendritic cells form over-active microtubule organizing centers, which cluster during dendritic cell-T cell interactions and, unlike in T cells, localize close to the cell center. Perturbing either centrosome integrity or centriole numbers and configuration in dendritic cells results in impaired T cell activation. Collectively, our results highlight a crucial role for centriole amplification and optimal centrosome positioning in antigen-presenting cells for controlling T cell responses.

Centrosome dynamics play a central role in immune regulation. Here, the authors demonstrate that centrosome integrity as well as centriole numbers and spatial organisation emerge as critical determinants of effective T cell responses.

## Full-text entities

- **Genes:** Fcgr2b (Fc receptor, IgG, low affinity IIb) [NCBI Gene 14130] {aka CD32, F630109E10Rik, Fc[g]RII, FcgRII, Fcgr2, Fcgr2a}, Pcnt (pericentrin (kendrin)) [NCBI Gene 18541] {aka KEN, Pcnt2, kendrin, m239Asp, m275Asp}, Fcgr3 (Fc receptor, IgG, low affinity III) [NCBI Gene 14131] {aka CD16}, Slc40a1 (solute carrier family 40 (iron-regulated transporter), member 1) [NCBI Gene 53945] {aka Dusg, Fpn1, IREG1, MTP, MTP1, Ol5}, Tnfrsf4 (tumor necrosis factor receptor superfamily, member 4) [NCBI Gene 22163] {aka ACT35, CD134, Ly-70, Ox40, TXGP1L, Txgp1}, Foxp3 (forkhead box P3) [NCBI Gene 20371] {aka JM2, scurfin, sf}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Sell (selectin, lymphocyte) [NCBI Gene 20343] {aka CD62L, L-selectin, LAM-1, LECAM-1, LECAM1, Lnhr}, Kifc1 (kinesin family member C1) [NCBI Gene 100502766] {aka 100042970, Gm4137, HSET, KNSL2, Kifc5a, Knsl2a}, Tcrb (T cell receptor beta chain) [NCBI Gene 21577] {aka TCRbeta, Tib}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Cetn2 (centrin 2) [NCBI Gene 26370] {aka 1110034A02Rik, Calt, caltractin}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, Ccl5 (C-C motif chemokine ligand 5) [NCBI Gene 20304] {aka MuRantes, RANTES, SISd, Scya5, TCP228}, Parp1 (poly (ADP-ribose) polymerase family, member 1) [NCBI Gene 11545] {aka 5830444G22Rik, ARTD1, Adprp, Adprt1, PARP, PPOL}, Nr4a1 (nuclear receptor subfamily 4, group A, member 1) [NCBI Gene 15370] {aka GFRP1, Gfrp, Hbr-1, Hbr1, Hmr, N10}, Cep250 (centrosomal protein 250) [NCBI Gene 16328] {aka B230210E21Rik, Cep2, Inmp}, Crocc (ciliary rootlet coiled-coil, rootletin) [NCBI Gene 230872], H2 (histocompatibility-2, MHC) [NCBI Gene 111364] {aka H-2, MHC-II}, Tbp (TATA box binding protein) [NCBI Gene 21374] {aka GTF2D1, Gtf2d, SCA17, TFIID}, Cdk5rap2 (CDK5 regulatory subunit associated protein 2) [NCBI Gene 214444] {aka 2900018K03Rik, an, mKIAA1633}, Serpinb1-ps1 (serine (or cysteine) peptidase inhibitor, clade B, member 1, pseudogene) [NCBI Gene 282665] {aka EID, ovalbumin}, Plk4 (polo like kinase 4) [NCBI Gene 20873] {aka 1700028H20, Sak, Stk18}, Cd69 (CD69 antigen) [NCBI Gene 12515] {aka 5830438K24Rik, AIM, VEA}, Csf2 (colony stimulating factor 2 (granulocyte-macrophage)) [NCBI Gene 12981] {aka CSF, Csfgm, GMCSF, Gm-CSf, MGI-IGM}, Cd19 (CD19 antigen) [NCBI Gene 12478], Itgax (integrin alpha X) [NCBI Gene 16411] {aka Cd11c, Cr4, N418}, Apc (APC, WNT signaling pathway regulator) [NCBI Gene 11789] {aka CC1, Min, mAPC}, Cxcl1 (C-X-C motif chemokine ligand 1) [NCBI Gene 14825] {aka Fsp, Gro1, KC, Mgsa, N51, Scyb1}, Cdc42 (cell division cycle 42) [NCBI Gene 12540]
- **Diseases:** MT (MESH:C567137), inflammatory (MESH:D007249), DC-T (MESH:D054221), cancer (MESH:D009369), T (MESH:D001260), BMDCs (MESH:D001855), IS (MESH:D007154)
- **Chemicals:** PFA (MESH:C003043), sucrose (MESH:D013395), LPS (MESH:D008070), agarose (MESH:D012685), PJ-34 (MESH:C434926), H2O (MESH:D014867), phenol (MESH:D019800), L-Glutamine (MESH:D005973), CO2 (MESH:D002245), sodium azide (MESH:D019810), DAPI (MESH:C007293), DMSO (MESH:D004121), ammonium persulfate (MESH:C031276), Centrinone (MESH:C000599097), ethanol (MESH:D000431), AA (MESH:D020106), calcium (MESH:D002118), ice (MESH:D007053), PBS (MESH:D007854), pretubulysin (MESH:C575012), ascorbic acid (MESH:D001205), Alexa Fluor 555 (MESH:C000608607), SDS (MESH:D012967), N, N'-methylenebisacrylamide (MESH:C021221), Alexa Fluor 647 (MESH:C569686), Penicillin (MESH:D010406), Parafilm (MESH:D010232), CFSE (-), phenol red (MESH:D010637), NaCl (MESH:D012965), sodium acrylate (MESH:C036658), T (MESH:D014316), Triton X-100 (MESH:D017830), Streptomycin (MESH:D013307), EDTA (MESH:D004492)
- **Species:** Cricetus cricetus (black-bellied hamster, species) [taxon 10034], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** DC-T — Mus musculus (Mouse), Conditionally immortalized cell line (CVCL_6B02), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), N — Homo sapiens (Human), Finite cell line (CVCL_UZ57), OT-II — Homo sapiens (Human), Lung small cell carcinoma, Cancer cell line (CVCL_7018)

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12804990/full.md

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Source: https://tomesphere.com/paper/PMC12804990