题目：Single cell analysis of antigen-specific T cell response against Mycobacterium tuberculosis
报告人：Huang Huang, Ph.D.（IMM优秀毕业生）
Institute for Immunity, Transplantation, and Infection, Stanford University, USA
Abstract: It is estimated that one-third of the world’s population is latently infected with M. tuberculosis (Mtb). While only 10% of the infected individuals develop progressive disease after exposure to Mtb. The mechanisms underlying protection against infection and/or disease are not well understood and there are no immunologic or other biomarkers known to predict the efficacy of vaccine candidates without the long and costly progression to Phase IIB clinical trials. In order to study the T cell response against Mtb, here we are using single-cell T cell receptor (TCR) sequencing to study the TCR repertoire of Mtb-reactive T cells and demonstrated in vivo clonal expansion, public TCR motifs and Th1* like phenotypes of Mtb-reactive T cells. We also developed and optimized a method to capture both TCR and transcriptome from the same single T cell with more than 80% successful rate in sorted single T cell. It thus allows functional study of T cell clones (cells with identical TCRs) directly from blood or other tissues without in vitro expansion. Using this method, we have identified conventional and unconventional (MAIT/NKT) cells reactive to Mtb. Transcriptome analysis of clonal expanded cells identified a feature of clonal senescence among conventional T cells but not among unconventional T cells.