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

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

Science translational medicine (2016-06-03)
Shu-Qi Zhang, Patricia Parker, Ke-Yue Ma, Chenfeng He, Qian Shi, Zhonghao Cui, Chad M Williams, Ben S Wendel, Amanda I Meriwether, Mary Alice Salazar, Ning Jiang
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Milli-Mark Anti-CD8 -FITC Antibody, clone DK25, clone DK25, Milli-Mark®, from mouse
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