Large-Scale HLA Tetramer Tracking of T Cells during Dengue Infection Reveals Broad Acute Activation and Differentiation into Two Memory Cell Fates

Melissa Hui Yen Chng, Mei Qiu Lim, Angeline Rouers, Etienne Becht, Bernett Lee, Paul A MacAry, David Chien Lye, Yee Sin Leo, Jinmiao Chen, Katja Fink, Laura Rivino, Evan W Newell

Research output: Contribution to journalArticle (Academic Journal)peer-review

7 Citations (Scopus)
34 Downloads (Pure)

Abstract

T cells play important multifaceted roles during dengue infection, and understanding their responses is important for defining correlates of protective immunity and identifying effective vaccine antigens. Using mass cytometry and a highly multiplexed peptide-HLA (human leukocyte antigen) tetramer staining strategy, we probed T cells from dengue patients-a total of 430 dengue and control candidate epitopes-together with key markers of activation, trafficking, and differentiation. During acute disease, dengue-specific CD8+ T cells expressed a distinct profile of activation and trafficking receptors that distinguished them from non-dengue-specific T cells. During convalescence, dengue-specific T cells differentiated into two major cell fates, CD57+ CD127--resembling terminally differentiated senescent memory cells and CD127+ CD57--resembling proliferation-capable memory cells. Validation in an independent cohort showed that these subsets remained at elevated frequencies up to one year after infection. These analyses aid our understanding of the generation of T cell memory in dengue infection or vaccination.

Original languageEnglish
Pages (from-to)1119-1135.e5
Number of pages23
JournalImmunity
Volume51
Issue number6
Early online date19 Nov 2019
DOIs
Publication statusPublished - 17 Dec 2019

Keywords

  • mass cytometry
  • cytof
  • dengue
  • T cell
  • memory
  • CD57
  • IL-7R
  • CD127
  • DENV
  • tetramer

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