LANA-specific CD4+ effector T cells accumulate at the site of KSHV infection in humanized mice
Kaposi's sarcoma-associated herpesvirus (KSHV) infection is linked with the development of life-threatening malignancies in elderly and immunocompromised hosts, suggesting tight control of the infection by T cell responses. T cells against KSHV, however, are barely detectable in infected individuals, and the mechanisms underlying immune recognition of KSHV-infected cells remain poorly understood. Here, we present publicly available sequences of T cell receptors (TCRs) targeting the KSHV latency-associated nuclear antigen (LANA/ORF73). By using these TCRs transgenically expressed on T cells as identifiers for KSHV-specific cells, we show that despite their failure to recognize KSHV-infected B cells in vitro, activated effector memory differentiated LANA-specific CD4<sup>+</sup> T cells accumulate in vivo at infection sites in the preclinical infection model of humanized mice. This suggests more efficient antigen-presentation in vivo than by KSHV-infected B cells in vitro and highlights the possible contribution of CD4<sup>+</sup> T cells to the immunosurveillance of latently infected B cells.
Authors
- Danusia Vanoaica
- Svenja L. Nopper
- Hans J. Stauss (ORCID: https://orcid.org/0000-0003-4340-7911)
- Alma Delia Valencia-Camargo (ORCID: https://orcid.org/0009-0005-3130-9910)
- Lisa Rieble (ORCID: https://orcid.org/0000-0001-9773-8607)
- Christian Münz (ORCID: https://orcid.org/0000-0001-6419-1940)
- Sandra L. Schmid (ORCID: https://orcid.org/0000-0002-1690-7024)
- Michelle Böni (ORCID: https://orcid.org/0000-0002-7829-258X)
- Angelika Holler
- Shitao Peng
- Kareem Haal (ORCID: https://orcid.org/0009-0006-8868-1665)
Institutions
- University of Zurich (CH)
- Karolinska Institutet (SE)
- Medizinische Hochschule Hannover (DE)
- ETH Zurich (CH)
- Institute of Infection and Immunity (CA)
- University College London (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-05
- DOI
- https://doi.org/10.1038/s41467-025-66992-2
- Primary Topic
- Viral-associated cancers and disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- Pfizer
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Eidgenössische Technische Hochschule Zürich
- Universität Zürich
- Schweizerische Akademie der Medizinischen Wissenschaften
- Swiss Vaccine Research Institute
- Roman, Marga und Mareille Sobek Stiftung
- Staatssekretariat für Bildung, Forschung und Innovation
- Functional Genomics Center Zurich