Research ArticleImmunology

Direct measurement of T cell receptor affinity and sequence from naïve antiviral T cells

Science Translational Medicine  01 Jun 2016:
Vol. 8, Issue 341, pp. 341ra77
DOI: 10.1126/scitranslmed.aaf1278

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iTAST: A taste of T cell specificity

There is a well-established link between T cell receptor (TCR) affinity and T cell function, which can have important implications for T cell–based therapies. Zhang et al. have now developed a method to concurrently sequence TCRs and measure TCR affinity of individual T cells from humans. Using this technique, they show that older individuals may be less able to respond to viral infections or vaccines due to a lack of high-affinity T cells. This method could help screen T cells for cancer immunotherapy or vaccine responses.

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.

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