Generation and characterization of a novel MHC-II tetramer for tracking and characterization of toxin B–specific CD4+ T cell responses
Rattachement africain : us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
The gastrointestinal pathogen Clostridioides difficile is a major burden for health systems due to high rates of recurrence. C. difficile pathogenesis is mediated by two virulence factors, toxin A (TcdA) and toxin B (TcdB). Antibodies specific for TcdA and TcdB are correlated with protection from symptomatic recurrence; however, the role for CD4+ T cells is poorly understood in part due to the lack of tools to study the toxin-specific CD4+ T cell response. Our group recently demonstrated the antibody and CD4+ T cell response to C. difficile toxins is impaired via the glucosyltransferase activity of the toxins; however, tools do not exist to study the protective capacity and the phenotype of toxin-specific CD4+ T cells. Therefore, we developed a major histocompatibility complex class II (MHC-II) tetramer to identify TcdB-specific CD4+ T cells via flow cytometry. Herein, we identified an immunodominant epitope (TcdB1961-1975) in the CROPs region of TcdB and optimized an MHC-II tetramer for use in tracking and phenotyping TcdB-specific CD4+ T cell responses following multiple different immunization strategies in mice. Utilizing the tetramer, TcdB-specific T follicular helper cells were detected following TcdB-CROPs messenger RNA lipid nanoparticle vaccination validating the advantage of the tetramer. Furthermore, using a modular messenger RNA vector expressing the TcdB1961 peptide covalently bound to the beta chain of MHC-II, we were able to generate a robust population of TcdB-specific CD4+ T cells. These data outline the generation of new tools for the C. difficile field and lay the groundwork for future studies of toxin-specific CD4+ T cell responses.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Generation and characterization of a novel MHC-II tetramer for tracking and characterization of toxin B–specific CD4+ T cell responses
- Date Crossref
- 01/08/2026
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
RTOG Foundation pays non établi dans la noticeOrganisation à but non lucratif
-
Graduate Hospital pays non établi dans la noticeÉtablissement de santé
-
University of Pennsylvania Immunology Graduate Group pays non établi dans la noticeUniversité ou école supérieure
-
Children's Hospital of Philadelphia Center for Microbial Medicine pays non établi dans la noticeOrganisme public
-
Drexel University Department of Medicine pays non établi dans la noticeUniversité ou école supérieure
-
Penn Center for AIDS Research pays non établi dans la noticeStructure de recherche
-
Parker Institute for Cancer Immunotherapy pays non établi dans la noticeStructure de recherche
-
Perelman School of Medicine Department of Microbiology pays non établi dans la noticeUniversité ou école supérieure
-
Department of Pathology and Laboratory Medicine pays non établi dans la noticeStructure de recherche
RTOG Foundation, Graduate Hospital et Immunology Graduate Group — University of Pennsylvania, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.