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

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.