title: Direct measurement of T cell receptor affinity and sequence from naïve antiviral T cells.
abstract: T cells recognize and kill a myriad of pathogen-infected or cancer cells using a diverse set of T cell receptors (TCRs). The affinity of TCR to cognate antigen is of high interest in adoptive T cell transfer immunotherapy and antigen-specific T cell repertoire immune profiling because it is widely known to correlate with downstream T cell responses. We introduce the in situ TCR affinity and sequence test (iTAST) for simultaneous measurement of TCR affinity and sequence from single primary CD8(+) T cells in human blood. We demonstrate that the repertoire of primary antigen-specific T cells from pathogen-inexperienced individuals has a surprisingly broad affinity range of 1000-fold composed of diverse TCR sequences. Within this range, samples from older individuals contained a reduced frequency of high-affinity T cells compared to young individuals, demonstrating an age-related effect of T cell attrition that could cause holes in the repertoire. iTAST should enable the rapid selection of high-affinity TCRs ex vivo for adoptive immunotherapy and measurement of T cell response for immune monitoring applications.
authors.affiliation: McKetta Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Shu-Qi
authors.initials: SQ
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Parker
authors.affiliation: Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Ke-Yue
authors.initials: KY
authors.lastname: Ma
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Chenfeng
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Zhonghao
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Chad M
authors.initials: CM
authors.lastname: Williams
authors.affiliation: McKetta Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Ben S
authors.initials: BS
authors.lastname: Wendel
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Amanda I
authors.initials: AI
authors.lastname: Meriwether
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Mary Alice
authors.initials: MA
authors.lastname: Salazar
authors.affiliation: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA. Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA. jiang@austin.utexas.edu.
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D016174:Hepacivirus / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell