Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 8, Issue 341, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aaf1278
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Funding
- NIH [R00AG040149]
- Cancer Prevention and Research Institute of Texas [R1120]
- Welch Foundation [F1785]
- Damon Runyon-Rachleff Innovator Award [DRR-32-15]
- Thrust 2000-Archie W. Straiton Endowed Graduate Fellowship in Engineering
- Thrust 2000-George Sawyer Endowed Graduate Fellowship in Engineering
- Virginia and Ernest Cockrell Jr. Scholarship in Engineering
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T cells recognize and kill amyriad 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.
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