bims-maitce 2026-07-05 papers

Issue of 2026–07–05
six papers selected by
Andy E. Hogan, Maynooth University

Nat Commun. 2026 Jun 29.

Human neonatal MR1T cells have more diverse TCR repertoires but reduced bacterial recognition than adult MR1T cells.

Dylan Kain, Wael Awad, G W McElfresh, Meghan Cansler, Gwendolyn M Swarbrick, Kean Chan Yew Poa, Conor McNeice, Gregory Boggy, Katherine H Rott, Megan D Null, David M Lewinsohn, Jamie Rossjohn, Benjamin N Bimber, Deborah A Lewinsohn.

Bacterial sepsis is a leading cause of neonatal mortality. Pro-inflammatory MR1-restricted T (MR1T) cells may help protect from sepsis by recognizing bacterial pathogens producing the canonical MR1 antigen 5-OP-RU. Most adult MR1T cells are mucosal-associated invariant T (MAIT) cells expressing a semi-invariant TCRα, while neonatal MR1T cells express diverse TCRα chains. Here, we perform combined single-cell RNA-sequencing and TCR repertoire analyses on MR1/5-OP-RU tetramer-positive cells from neonatal cord blood (CB) and adult blood. Compared to adult MR1T cells, CB MR1T cells exhibit greater TCR diversity, reduced cytotoxic and proinflammatory gene expression, diminished bacterial recognition and reduced binding to MR1/5-OP-RU. Structural analysis of a CB MAIT TCR reveals decreased β chain contribution to the TCR-MR1 interface relative to an adult MAIT TCR. These findings demonstrate developmental stage-specific differences in MR1T cell repertoire, function and MAIT TCR structure with implications for neonatal sepsis.

DOI: https://doi.org/10.1038/s41467-026-74998-7

Front Immunol. 2026 ;17 1822615

Immunological profiling of rheumatoid factor-positive primary Sjögren's syndrome by single-cell RNA sequencing.

Yifei Wang, Wenqi Ji, Fei Teng, Yuxin Han, Heng Xu, Yuxing Zhi, Qingwen Tao, Guangyao Chen.

Objective: Primary Sjögren's syndrome (pSS) is a highly heterogeneous autoimmune disease. Previous studies have suggested that rheumatoid factor (RF)-positive patients appear to have a higher incidence of systemic involvement. However, the underlying mechanisms remain unclear. This study aims to elucidate the potential biological mechanisms through single-cell RNA sequencing (scRNA-seq).
Methods: Peripheral blood mononuclear cells from 3 healthy controls, 6 RF-negative (RF-) pSS patients, and 6 RF-positive (RF+) pSS patients were subjected to scRNA-seq. Subsequent analyses included pathway enrichment analysis, trajectory analysis, cell-cell communication analysis, and B cell receptor (BCR) and T cell receptor (TCR) repertoire profiling. Potential differences were further validated by flow cytometry.
Results: Analysis of B cell subsets revealed a significantly increased proportion of plasma cells in RF+ patients, and differential gene expression analysis indicated enhanced pathways related to antibody production, clonal expansion, and type I interferon activation. In T-cell subsets, the RF+ group showed a notably higher proportion of CD8+ T cells, which exhibited stronger cytotoxicity and activation of interferon signaling. In contrast, mucosal-associated invariant T (MAIT) cells demonstrated activated interferon signaling but were present at a lower proportion compared to the RF- group. Cell-cell communication analysis revealed strengthened crosstalk between B cells and T cells in the RF+ group. Pseudo-time trajectory analysis further indicated that in RF+ patients, both plasma cells and CD8+ T cells exhibited a developmental skew toward a terminally differentiated state. Additionally, both BCR and TCR repertoire analyses indicated RF+ and RF- patients exhibiting distinct patterns in clonal distribution and frequency. Flow cytometry further validated the increased proportion of CD8+ T cells and the decreased proportion of MAIT cells in the peripheral blood of RF+ pSS patients.
Conclusion: The RF status in pSS patients is closely associated with specific immune cell profiles. RF+ patients exhibit more active plasma cell responses, enhanced CD8+ T-cell cytotoxicity and interferon responses, as well as heightened interferon signaling yet reduced proportion of MAIT cells. RF status serves as a key stratification marker for immune heterogeneity in pSS patients, providing new insights for understanding disease mechanisms and developing targeted therapeutic strategies.

Keywords: cell communication; primary Sjögren’s syndrome; pseudo-time analysis; rheumatoid factor; single-cell RNA sequencing

DOI: https://doi.org/10.3389/fimmu.2026.1822615

J Immunol. 2026 Jun 07. pii: vkag094. [Epub ahead of print]215(6):

An MR1-specific nanobody capable of blocking MR1T cell activation.

Timothy A Bates, Corinna A Kulicke, Sintayehu K Gurmessa, Se-Jin Kim, Sushant Suresh, Jules B Reyes-Weinstein, Audrey Hinchliff, John E Burke, David M Lewinsohn, Fikadu G Tafesse.

MR1 is a non-polymorphic, ubiquitously expressed, MHC class I-like antigen-presenting molecule that presents small-molecule metabolites to T cells. Studies have shown that MR1 plays a role in microbial infection, inflammation, and tumor immunity. The antigens it presents include metabolites of microbial and self-origin as well as small-molecule drugs and form stable complexes with MR1 that are displayed on the cell surface to activate T cells. However, unlike classical MHC I and II molecules, the fundamental biology of MR1 remains poorly understood, particularly the mechanisms governing antigen loading and intracellular trafficking. This knowledge gap is largely due to the lack of molecular tools available to precisely manipulate MR1 function. In this study, we describe a high-affinity (1.6 nM KD) anti-MR1 nanobody, MR1Nb1. We characterize the binding of this nanobody including affinity by ELISA and kinetics by BLI. Crucially, we map the binding epitope of MR1Nb1 on MR1 by HDX-MS, providing key insights into the mechanism through which it blocks MR1T cell activation. In functional assays MR1Nb1 effectively and specifically blocks MR1T cell activation by cells infected with M. tuberculosis or treated with M. smegmatis supernatant or the synthetic ligand deazalumazine. MR1Nb1 further stains MR1-ligand complexes on the cell surface in a flow cytometry assay. This nanobody represents a unique and versatile tool for the field, as it can be produced inexpensively and expressed intracellularly within antigen presenting cells. Hence, our study provides a powerful new molecular probe for dissecting the mechanistic underpinnings of MR1 biology and uncover its broader roles in immunity.

Keywords: MR1; T cells; nanobody

DOI: https://doi.org/10.1093/jimmun/vkag094

Front Immunol. 2026 ;17 1900363

Editorial: Exploring unconventional T cells and CAR-T-cells in cancer immunotherapy.

Laura Patrussi, Chenran Zhang.

Keywords: CAR T cell; MAIT (mucosal-associated invariant T) cell; gamma delta T (γδ T) cells; iNKT (invariant natural killer T cell); tumor microenvironment - TME; unconventional T cell

DOI: https://doi.org/10.3389/fimmu.2026.1900363

Cell Mol Gastroenterol Hepatol. 2026 Jul 03. pii: S2352-345X(26)00124-4. [Epub ahead of print] 101846

Focus on MAIT cell antigens fueling biliary liver injury.

Josias J Mürle, Magdalena Filipowicz Sinnreich.

DOI: https://doi.org/10.1016/j.jcmgh.2026.101846

Front Microbiol. 2026 ;17 1815566

Research progress on T-cell responses in Staphylococcus aureus infections.

Xupeng Li, Ruidan Wang, Wentong Yan, Jiarui Guan, Haibang Pan, Bo Wang.

Introduction: Staphylococcus aureus is a common Gram-positive pathogen capable of causing a wide range of severe infections. T cells are key adaptive immune effectors in S. aureus infection, and their response patterns and functional states strongly influence bacterial clearance, inflammatory regulation, and clinical outcomes.
Methods: This narrative review summarizes recent evidence on T-cell responses in S. aureus infection, with emphasis on major T-cell subsets, context-dependent immune dysregulation, immune evasion, immunopathology, and potential immunoregulatory strategies.
Results: Current evidence indicates that Th1/Th17 responses contribute to antimicrobial defense, whereas regulatory T cells may limit inflammatory damage but may also favor chronic colonization. Across different infection sites and disease stages, CD8+ T cells and innate-like T-cell populations, including γδ T cells, MAIT cells, and NKT cells, display marked functional heterogeneity. Recent advances in single-cell omics, immunometabolism, and immune checkpoint research have further clarified the dynamic changes in T-cell responses during S. aureus infection.
Discussion: T-cell responses in S. aureus infection are highly context-dependent. A better understanding of these immune programs may inform future prevention and treatment strategies, including vaccines and targeted immunomodulatory interventions.

Keywords: Staphylococcus aureus; T-cell dysregulation; T-cell response; immune evasion; immunoregulatory strategies

DOI: https://doi.org/10.3389/fmicb.2026.1815566