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<p>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.</p>

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LANA-specific CD4+ effector T cells accumulate at the site of KSHV infection in humanized mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月5日

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  • Michelle Böni,
  • Shitao Peng,
  • Danusia Vanoaica,
  • Kareem Haal,
  • Svenja L. Nopper,
  • Lisa Rieble,
  • Sandra Schmid,
  • Alma Delia Valencia-Camargo,
  • Angelika Holler,
  • Hans Stauss,
  • Christian Münz

摘要

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+ 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+ T cells to the immunosurveillance of latently infected B cells.