Convergence, plasticity, and tissue residence of regulatory T cell response via TCR repertoire prism

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F24%3A00138874" target="_blank" >RIV/00216224:14740/24:00138874 - isvavai.cz</a>

Result on the web

<a href="https://elifesciences.org/articles/89382" target="_blank" >https://elifesciences.org/articles/89382</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.7554/eLife.89382" target="_blank" >10.7554/eLife.89382</a>

Result language

angličtina

Original language name

Convergence, plasticity, and tissue residence of regulatory T cell response via TCR repertoire prism

Original language description

Suppressive function of regulatory T cells (Treg) is dependent on signaling of their antigen receptors triggered by cognate self, dietary, or microbial peptides presented on MHC II. However, it remains largely unknown whether distinct or shared repertoires of Treg TCRs are mobilized in response to different challenges in the same tissue or the same challenge in different tissues. Here we use a fixed TCR beta chain FoxP3-GFP mouse model to analyze conventional (eCD4) and regulatory (eTreg) effector TCR alpha repertoires in response to six distinct antigenic challenges to the lung and skin. This model shows highly 'digital' repertoire behavior with easy-to-track challenge-specific TCR alpha CDR3 clusters. For both eCD4 and eTreg subsets, we observe challenge-specific clonal expansions yielding homologous TCR alpha clusters within and across animals and exposure sites, which are also reflected in the draining lymph nodes but not systemically. Some CDR3 clusters are shared across cancer challenges, suggesting a response to common tumor-associated antigens. For most challenges, eCD4 and eTreg clonal response does not overlap. Such overlap is exclusively observed at the sites of certain tumor challenges, and not systematically, suggesting transient and local tumor-induced eCD4=&gt;eTreg plasticity. This transition includes a dominant tumor-responding eCD4 CDR3 motif, as well as characteristic iNKT TCR alpha CDR3. In addition, we examine the homeostatic tissue residency of clonal eTreg populations by excluding the site of challenge from our analysis. We demonstrate that distinct CDR3 motifs are characteristic of eTreg cells residing in particular lymphatic tissues, regardless of the challenge. This observation reveals the tissue-resident, antigen-specific clonal Treg populations.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10600 - Biological sciences

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

elife

ISSN

2050-084X

e-ISSN

—

Volume of the periodical

12

Issue of the periodical within the volume

apr

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

1-14

UT code for WoS article

001199839100001

EID of the result in the Scopus database

—