TCR and BCR Repertoire

Project Title: Composition of T- and B-Cell Repertoire and Mapping of Virus-Specific T-Cell Receptor Sequences

NIAID Principal Investigator: Luigi Notarangelo, M.D.
Chief, Laboratory of Clinical Immunology and Microbiology
Chief, Immune Deficiency Genetics Section, LCIM

How does the adaptive immune system respond to COVID-19 infection over time?

The Immune Deficiency Genetics Section aims to analyze the dynamic changes that occur within an individual’s T-cell and B-cell repertoires during the transition from acute COVID-19 infection into convalescence. Using the immunoSEQ assay for high-throughput sequencing of immune repertoires, they will identify which T- and B-cell clonotypes are expanding, track clonotype populations through the course of disease, and identify antigen-specific clones indicative of memory T-cell responses. In partnership with Adaptive’s ImmuneCODE program, the Immune Deficiency Genetics Section will work to uncover the T-cell receptor signature of immune response to COVID-19. Additionally, with the collaboration of John Tsang, Ph.D. (NIAID), CITE-Seq and single cell ATAC-Seq sequencing methods could be combined on these longitudinal samples to elucidate how the transcriptome and epigenomics of individual cells changes over the course of infection. In collaboration with Doug Kuhns, Ph.D. (NCI), variations of adaptive immune responses will be correlated with changes in serum levels of a large array of cytokines and chemokines. Together, these studies will provide a deeper understanding of how the adaptive immune system reacts and responds to acute infection with COVID-19, an essential step in developing immunological memory to prevent reinfection.

Participating Groups

NIAID

• John Tsang, Ph.D.

Frederick National Laboratory for Cancer Research

• Douglas B. Kuhns, Ph.D.

Commercial Biotech

• Ian Kaplan, Adaptive Biotechnologies

Sample Requirements

Whole blood (2.5 mL), frozen at -20˚C. This project will require longitudinal sampling (3-5) for each patient. Ideally, samples would be taken 1) upon hospital admission, 2) during hospitalization, 3) at discharge, and 4) after discharge.

For CITE-Seq and scATAC-Seq studies, 2 million cryopreserved PBMC, or 2 mL of EDTA-blood pellet resuspended vol/vol in fetal bovine serum + 20% DMSO, and frozen at -80˚C are required. Ideally, samples would be taken 1) upon hospital admission, 2) during hospitalization, 3) at discharge, and 4) after discharge.

For serological studies (cytokine/chemokine levels), 0.5 mL of serum or plasma is required. Ideally, samples would be taken 1) upon hospital admission, 2) during hospitalization, 3) at discharge, and 4) after discharge.