V-CARMA: A tool for the detection and modification of antigen-specific T cells.
Xi-Zhi J GuoStephen J ElledgePublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
T cells promote our body's ability to battle cancers and infectious diseases but can act pathologically in autoimmunity. The recognition of peptides presented by major histocompatibility complex (pMHC) molecules by T cell receptors (TCRs) enables T cell-mediated responses. To modify disease-relevant T cells, new tools to genetically modify T cells and decode their antigen recognition are needed. Here, we present an approach using viruses pseudotyped with peptides loaded on MHC called V-CARMA (Viral ChimAeric Receptor MHC-Antigen) to specifically target T cells expressing cognate TCRs for antigen discovery and T cell engineering. We show that lentiviruses displaying antigens on human leukocyte antigen (HLA) class I and class II molecules can robustly infect CD8 + and CD4 + T cells expressing cognate TCRs, respectively. The infection rates of the pseudotyped lentiviruses (PLVs) are correlated with the binding affinity of the TCR to its cognate antigen. Furthermore, peptide-HLA pseudotyped lentivirus V-CARMA constructs can identify target cells from a mixed T cell population, suppress PD-1 expression on CD8 + T cells via PDCD1 shRNA delivery, and induce apoptosis in autoreactive CD4 + T cells. Thus, V-CARMA is a versatile tool for TCR ligand identification and selective T cell manipulation.
Keyphrases
- infectious diseases
- heat shock
- endothelial cells
- oxidative stress
- sars cov
- poor prognosis
- binding protein
- small molecule
- endoplasmic reticulum stress
- signaling pathway
- high throughput
- young adults
- immune response
- mass spectrometry
- peripheral blood
- cancer therapy
- quantum dots
- label free
- genetic diversity
- heat stress
- induced pluripotent stem cells
- wound healing
- celiac disease