High throughput method for screening for homologous t cells and epitope reactivity in primary human cells

Abstract

An assay for autologous primary immune cells is described in which the blood cells of an individual can be functionally screened simultaneously against individual antigens of interest, such as T cell epitopes, without HLA haplotype-specific agents. The antigen reactivity is associated with individual T cells using an oligonucleotide labeled hash tracking system followed by deconvolution by single cell sequencing.

Description

[0001] Cross References to Related Applications [0002] This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application Serial No. 62 / 910,379, filed October 3, 2019, the disclosure of which is incorporated herein by reference in its entirety. [0003] References to Sequence Listings Submitted as Text Files via EFS WEB [0004] The sequence listing written in file 10669_ST25.txt is 5 kilobytes, created on October 2, 2020, and is hereby incorporated by reference. Background technique [0005] With growing interest in antigen-specific T cell activity in human disease, there is a need to be able to associate epitope-specific TCR sequences with cognate epitopes presented in the context of HLA. However, identifying which epitopes lead to activation of productive T cells and the TCR sequences of responding T cells has historically been and continues to be a technically challenging task. [0006] Traditional methods used to assess antigen-specific T-...

AI Technical Summary

Problems solved by technology

While these methods are useful, they may require expensive individual HLA haplotype-specific reagents (multimers) and large amounts of blood for high-throughput assessment of potential reactivity

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