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­­Delineating the role of co-stimulatory signals on human virus-specific memory CD8+ T cell activation and expansion using highly selective T cell receptor-targeted biologics

GSE312389 Homo sapiens (human) RNA-seq (gene expression) 20 samples Submitted 2025/12/08 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 20 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
20 samples: 8 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
T-cell receptor/CD28-targeted immunotherapeutics selectively drive naive T-cell expansion to generate functional HIV-specific responsesJournal of virology · 2025
Summary (written by the submitters)
To delineate the minimum signals required to activate and expand antigen-specific memory CD8+ T cells, we recapitulated the discrete activation signals delivered by antigen-presenting cells using antigen-specific T-cell receptor-specific biologics termed Immuno-STAT (IST), which can specifically deliver a T cell receptor (TCR) signal alone or paired with a defined co-stimulatory signal to antigen-specific CD8+ T cells.
Read the full summary ↓
Using a reductionist approach that provides defined TCR and co-stimulatory signaling, we demonstrated that different IST could engage TCR alone or in combination with either CD28 or 4-1BB to initiate distinct transcriptional programs in memory CMV-specific CD8+ T cells. As compared to activation by TCR signaling alone, the combination of TCR and CD28 or 4-1BB co-stimulatory signals significantly altered the transcriptome and drove expression of genes related to growth and survival. Nevertheless, TCR signaling in the presence of IL-2 (5 U/ml) was sufficient for robust recall activation and expansion of functional cytomegalovirus CMV(NLV)-specific and HIV(SL9)-specific memory CD8+ T cells. This response contrasts with naïve CD8+ T cells, which required CD28 co-stimulation in addition to TCR stimulation for antigen-specific activation and expansion even in the presence of high levels of IL-2 (100 U/ml). These results have important implications for antigen-specific immunotherapy by indicating that biologics that deliver TCR signals alone in the presence of IL-2 may be sufficient for immunotherapeutic strategies designed to expand memory CD8+ T cells to eliminate cancerous or infected cells. In contrast, strategies that aim to stimulate naïve T cell responses may benefit from the codelivery of TCR and CD28 signals.
Published in
T-cell receptor/CD28-targeted immunotherapeutics selectively drive naive T-cell expansion to generate functional HIV-specific responses
Mueller AL, Lamcaj S, Garforth S et al. · Journal of virology 2025 · PMID 40762498 · doi:10.1128/jvi.00188-25
This dataset
Open GSE312389 in finder → Find more human RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE312389_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1373230 and SRA study SRP651081. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40762498) ↗
Study design
8 conditions, mostly in triplicate
NLVspecific T cells, NLVantiCD28, Day1, ×3 NLVspecific T cells, NLV41BBL, Day1, ×3 NLVspecific T cells, NLVFLAG, Day1, ×3 NLVspecific T cells, No Treat Control, Day1, ×3 NLVspecific T cells, No Treat Control, Day5, ×2 NLVspecific T cells, NLVFLAG, Day5, ×2 NLVspecific T cells, NLV41BBL retreat, Day5, ×2 NLVspecific T cells, NLVFLAG retreat, Day5, ×2

Supports a between-group comparison across 20 samples.

How we read this: 8 replicated groups read from 20 sample titles; they account for 20 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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