Clone tracking through repeated malaria reveals high-fidelity CD4+ memory responses

Few studies have assessed the clonality and functional fidelity of human CD4+ T cells responding to repeated infections in vivo. We utilized broad, longitudinal single-cell RNA and TCR tracking to study the functional stability and memory potential of thousands of CD4+ T cell clonotypes through repeated Plasmodium falciparum (Pf) infections over the course of hundreds of days. Strikingly, nearly all memory CD4+ T cell clonotypes displayed a strong preference for one of seven different subsets—Tcm, Th1, cytotoxic Th1, Th2, Th17, Treg, and Tr1. This phenomenon, which we call “clonal fidelity,” was influenced by clonal expansion, demonstrating an in vivo relationship between T cell polarization and proliferation. Using clone tracking, we characterized subset-specific trajectories of CD4+ T cell activation and identified clonotypes with specific reactivity to Plasmodium falciparum (Pf) blood-stage antigens. Tr1 cells, a peripherally-induced regulatory subset distinct from FOXP3+ Tregs, acco..., These processed data files are seurat objects that were generated from raw data available from NCBI (BioProject PRJNA1129481).
The code used to generate these files is available on GitHub (jason-nideffer/clone-tracking-in-malaria).
These files can be used (in conjunction with code available on GitHub) to reproduce the figures in the manuscript titled: \"Clone tracking through repeated malaria reveals high-fidelity CD4+ memory responses.\", , # Data from: Clone tracking through repeated malaria reveals high-fidelity CD4+ memory responses

[https://doi.org/10.5061/dryad.59zw3r2jw](https://doi.org/10.5061/dryad.59zw3r2jw)

## Description of the data and file structure

These processed data files are Seurat objects that were generated from raw data available from NCBI (BioProject PRJNA1129481).

The code used to generate these files is available on GitHub (jason-nideffer/clone-tracking-in-malaria).

These files can be used (in conjunction with code available on GitHub) to reproduce the figures in the manuscript titled: \"Clone tracking through repeated malaria reveals high-fidelity CD4+ memory responses.\"

### Files and variables

#### File: rna_tcr_malaria_specific.rds

**Description:** seurat object containing single memory CD4+ T cells analyzed by RNA/TCRseq. This object is the product of a full data processing pipeline (GitHub: jason-nideffer/clone-tracking-in-malaria; Steps 1-11). The seurat object includes metadata on a pe..., We have received explicit consent from all study participants to publish de-identified metadata and data derived from biological samples.