T cell receptor sequencing identifies prior SARS-CoV-2 infection and correlates with neutralizing antibodies and disease severity

Abstract

Conflict of interest: RE, TMS, RMG, IMK, and DHM declare employment and equity ownership with Adaptive Biotechnologies. ALG declares consulting fees with Abbott; institutional support from Abbott, Merck, and Gilead; and family employment at Labcorp. HJZ and JMC declare employment and equity ownership with Microsoft Corporation. LB, TM, and HSR declare leadership, employment, and equity ownership with Adaptive Biotechnologies. DMK declares receipt of a reagent grant from Oxford Immunotec related to SARS-CoV-2 diagnostics.

Self-Reported Use of COVID-19 Immunologic Test Results to Inform Decisions About Daily Activities and COVID-19 Vaccination

“…In March 2021, T-Detect™ COVID became the first T-cellbased COVID-19 diagnostic to receive Emergency Use Authorization from the US Food and Drug Administration (FDA). This consumer-directed test identifies prior SARS-CoV-2 infection by using next-generation sequencing of whole blood samples to assess enrichment of SARS-CoV-2-specific T-cell receptors (TCRs) among the TCR repertoire [23,[26][27][28][29].…”

Immunosequencing of the T-cell receptor repertoire reveals signatures specific for diagnosis and characterization of early Lyme disease

“…Given the well-characterized roles of CD8+ and CD4+ T cells in viral control and clearance (34), it is not surprising that strong T-cell responses are elicited by SARS-CoV-2 and mediated by similar antigens and TCRs across individuals (29)(30)(31). While CD4+ T cells are known to differentiate into effector cell types with roles in promoting cellular and humoral immunity following many bacterial infections (35), the publicity of T-cell responses to bacterial pathogens has yet to be characterized.…”

“…While the diversity of TCR recombination means that most of these disease-specific TCRs are "private," or highly unique to one individual, part of the T-cell response to a disease is "public," with identical amino acid sequences observed across multiple individuals, particularly those with shared HLA backgrounds (27). The public, disease-associated TCRs can be identified using a case/control study design (28)(29)(30)(31) and matched to specific antigens through multiplex identification of antigen-specific TCRs (MIRA) (28,32). Because these public clones are antigen-and HLA-specific, enrichment of such clones serves as a signature of infection in a given HLA context (28,29).…”

“…Because these public clones are antigen-and HLA-specific, enrichment of such clones serves as a signature of infection in a given HLA context (28,29). This approach has been successful in identification of past infection by cytomegalovirus (CMV) (28) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (29,30,33).…”

“…While CD4+ T cells are known to differentiate into effector cell types with roles in promoting cellular and humoral immunity following many bacterial infections (35), the publicity of T-cell responses to bacterial pathogens has yet to be characterized. To better understand the utility of TCR immunosequencing in the context of bacterial infection, we leveraged the previously described case-control study design approach (28)(29)(30)(31) to characterize LD-specific TCRs and develop a classifier to aid in diagnosis of LD. We tested the performance of the classifier in case and control cohorts distinct from those used in classifier training and assessed the correlation between T-cell responses and clinical features of LD.…”