Evidence map›Paper›PMID 41376632›Full record

ArticleFrontiers in immunology2025

TCR repertoire of human cytotoxic CD4 T cells responding to betaherpesviruses HHV-6B and HCMV.

Aniuska Becerra-Artiles, Grant C Weaver, Peter O Oluoch, Lawrence J Stern

Abstract read
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Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Aniuska Becerra-ArtilesDepartment of Pathology, UMass Chan Medical School, Worcester, MA, United States.
Grant C WeaverDepartment of Pathology, UMass Chan Medical School, Worcester, MA, United States.
Peter O OluochDepartment of Microbiology, UMass Chan Medical School, Worcester, MA, United States.
Lawrence J SternDepartment of Pathology, UMass Chan Medical School, Worcester, MA, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: The role of CD4 T cells in the control of viral infections beyond their traditional helper activity has been increasingly recognized, and CD4 T cells with cytotoxic capacity have been reported for the nearly ubiquitous betaherpesviruses HCMV (human cytomegalovirus) and HHV-6B (human herpesvirus 6B). Objective: We sought to investigate the functional landscape of cytotoxic CD4 T cells responding to HHV-6B and HCMV epitopes presented by DRB1*03:01 and to identify public T-cell receptors (TCRs) (i.e., shared by multiple subjects). Approach: We tetramer-sorted epitope-specific CD4 T cells from healthy donors and performed RNA and TCR sequencing to assess functional profiles and identify TCR clonotypes. We evaluated the publicity of the repertoire and tested the functionality, epitope specificity, and sensitivity of selected public clonotypes. Results: Differential gene expression analysis comparing T cells expanded with HHV-6B and HCMV epitopes showed differences in their functional profiles, with the HCMV-expanded T cells displaying a more robust cytotoxic gene expression signature. Tens to hundreds of TCR clonotypes responding to HHV-6B or HCMV were identified in each subject. The TCR repertoires were dominated by private clonotypes in all subjects, but 3 public TCRα/β, along with 41 public TCRα and TCRβ clonotypes were identified. Some of these clonotypes and closely related variants were found in a substantial fraction of DRB1*03:01 subjects in datasets of total peripheral blood TCR repertoires. TCRs associated with two HHV-6B epitopes (U11.306-323 and U85.88-104) and one HCMV epitope (pp65.509-523) were cloned for validation and biochemical characterization. Using an Conclusions: CD4 T cells recognizing HHV-6B or HCMV exhibit cytotoxic signatures and can lyse antigen-pulsed target cells, with the HCMV-specific population exhibiting greater activity. The TCR repertoires of CD4 T cells recognizing HHV-6B or HCMV epitopes presented by DRB1*03:01 are broad but include public TCR clonotypes. These TCRs may be useful to monitor infection, reactivation under immunosuppressive conditions, and response to therapy.

Indexed as

CD4-Positive T-LymphocytesCytomegalovirusCytomegalovirus InfectionsHerpesvirus 6, HumanReceptors, Antigen, T-CellRoseolovirus InfectionsT-Lymphocytes, CytotoxicEpitopes, T-LymphocyteHumansEpitopes, T-LymphocyteReceptors, Antigen, T-Cellcytotoxic CD4 T cellsHCMVHHV-6Bpublic TCRsTCR repertoire

Identifiers

PMID41376632
PMCPMC12687561

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.