Volume 23 Issue 10, October 2022

m1A58 is a common tRNA modification that can influence protein translational efficiency. Here Liu et al. reveal that tRNA methylation controls in vivo T cell activation by enhancing translation of the key transcription factor Myc.

Current SARS-CoV-2 vaccine recipients differ in infection history and the magnitude of their elicited antibody response. A large human cohort distinguished by these parameters are queried for effector T cell subsets, memory B cells and ability to recognize epitopes from SARS-CoV-2 variants of concern.

Akin to adult stem cells, precursor exhausted T cells are hierarchically organized, with long-lived CD62L⁺ stem-like T cells at the apex of the system. The transcription factor c-Myb controls the formation, maintenance and therapeutic function of these cells, with important implications for their clinical utilization.

During T cell activation, tRNA-m¹A ‘writers’ TRMT61A and TRMT6 are upregulated to modify a group of early tRNA species and promote efficient translation of certain pre-cell-cycling proteins, thus ensuring rapid T cell proliferation and a timely adaptive immune response.

Immunotherapeutic targeting of the surface glycoprotein CD19 has markedly improved outcomes in patients with relapsed and refractory B cell progenitor acute lymphoblastic leukemia. Genome-wide CRISPR–Cas9 screening identifies modulators of CD19 mRNA processing that affect the abundance of the surface protein in human B cell leukemia cells, with the potential to improve antigen-directed immunotherapy efficacy.

The explosion of single-cell and systems approaches in immunology risks leaving the uninitiated behind. This guide to systems immunology is designed for immunologists who want an introduction to the area.

Aifantis and colleagues use leukemic cell lines to identify modulators of CD19 expression that have the potential to improve therapeutic strategies.

Naive T cells are quiescent but undergo dynamic changes upon antigenic activation. Li and colleagues show that upregulation of tRNA methyltransferase complex TRMT61A–TRMT6 and N¹-methyladenosine modification of tRNAs contribute to accelerated mRNA translation efficiency, in particular that of MYC protein, and are required for rapid T cell proliferation.

Pace and colleagues assessed the antibody titers, B cell and T cell memory response against SARS-COV-2 in mRNA-vaccinated individuals to show that reduced antibody titers combined with a distinctive memory T cell profile in low vaccine responders correlated with breakthrough infection.

Endosomal TLR7 and TLR9 recognize RNA and DNA ligands, respectively, and both signal via MyD88 yet appear to play opposing roles in autoimmunity. Shlomchik and colleagues examine this TLR ‘paradox’, reporting that TLR9 has two protective functions, including an as yet unidentified additional MyD88-independent signaling pathway that confers protection against autoimmunity.

Recent studies suggest that neutrophils can exhibit substantial function diversity. Here, Ostuni and colleagues perform immunophenotyping and transcriptome analysis to characterize the heterogeneity of human neutrophils, both under steady state and upon stress-induced conditions.

Zhang and colleagues use single-cell RNA sequencing on the nasal mucosa to identify cell subsets and molecules that specifically contribute to the pathogenesis of chronic rhinosinusitis subtypes.

Here, the authors use genome-scale in vivo CRISPR screens to look at immune evasion mechanisms across cancer models, showing that IFN-mediated upregulation of classical and non-classical MHC class I inhibitory checkpoints facilitate immune escape.