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

## TL;DR

The study shows that LANA-specific CD4+ T cells accumulate at KSHV infection sites in humanized mice, suggesting their role in immune surveillance despite being hard to detect in humans.

## Contribution

The study identifies TCRs targeting LANA and demonstrates in vivo accumulation of LANA-specific CD4+ T cells in a humanized mouse model.

## Key findings

- LANA-specific CD4+ effector T cells accumulate at KSHV infection sites in humanized mice.
- KSHV-specific CD4+ T cells fail to recognize infected B cells in vitro but show effective antigen presentation in vivo.
- The findings suggest CD4+ T cells may contribute to immunosurveillance of latently infected B cells.

## Abstract

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.

Karposi’s Sarcoma-associated herpesvirus (KSHV) infection is associated with malignancy in older infected humans. Here the authors characterise antigen presentation using a KSHV-specific CD4+ T cell-derived TCR in a mouse model and show that although KSHV-specific CD4+ T cells are difficult to detect in humans, antigen presentation is effective in vivo suggesting persistence and accumulation of these cells through antigen recognition.