High-throughput T cell receptor (TCR) sequence tracking reveals clonal intrinsic selection for skin resident T cells in human genital HSV-2 infection (MUC7P.771)

Abstract

Abstract T cells resident in the barrier surface have been implicated to play an important role in rapid control of invading pathogen. Human genital herpes infection is characterized by frequent bursts of reactivating HSV-2 virus and rapid containments of host immune responses in genital skin and mucosa surface, thus a valuable human disease model for deciphering tissue resident immunity in vivo. Previously, we showed that both CD4 and CD8 T cells persisted locally for prolonged time period after complete resolution of HSV-2 infection. To understand the mechanism of T-cell resident immunity in the barrier tissue, we used high-throughput TCR sequencing to investigate the persistence, breadth and clonality of TCR vβ repertoire in sequential biopsy tissues obtained during HSV-2 lesion evolution from active lesion, healed, to 2, 4, and 8 weeks post healing. Each tissue TCR vβ repertoire is consisted of thousands unique productive sequences, a diverse yet oligoclonal T-cell profile. Interestingly, high frequency TCRVβ sequences dominated in post-healed tissues were poorly represented in circulating T cells from the blood, vice versa was also true. Although hundreds of TCRVB sequences were found commonly shared among sequential biopsies in the same subjects, only a few clones showed increased persistence, emerging from low frequency in lesion to dominance in post healed tissue. These data suggest a T-cell intrinsic mechanism in dictating T cell survival and/or self-renewal in human tissue.