bims-maitce 2024-09-15 papers

Issue of 2024–09–15
two papers selected by
Andy E. Hogan, Maynooth University

J Biol Chem. 2024 Sep 09. pii: S0021-9258(24)02249-X. [Epub ahead of print] 107748

Impaired endocytosis and accumulation in early endosomal compartments defines herpes simplex virus-mediated disruption of the non-classical MHC class I-related molecule MR1.

Carolyn Samer, Hamish E G McWilliam, Brian P McSharry, James G Burchfield, Richard J Stanton, Jamie Rossjohn, Jose A Villadangos, Allison Abendroth, Barry Slobedman.

Presentation of metabolites by the Major Histocompatibility Complex Class-I-related protein 1 (MR1) molecule to Mucosal-Associated Invariant T (MAIT) cells is impaired during herpes simplex type 1 (HSV-1) and type 2 (HSV-2) infections. This is surprising given these viruses do not directly synthesise MR1 ligands. We have previously identified several HSV proteins responsible for rapidly downregulating the intracellular pool of immature MR1, effectively inhibiting new surface antigen presentation, while pre-existing ligand-bound mature MR1 is surprisingly upregulated by HSV-1. Using flow cytometry, immunoblotting and high throughput fluorescence microscopy we demonstrate that the endocytosis of surface MR1 is impaired during HSV infection, and that internalised molecules accumulate in EEA1-labelled early endosomes, avoiding degradation. We establish that the short MR1 cytoplasmic tail is not required for HSV-1 mediated downregulation of immature molecules, however it may play a role in the retention of mature molecules on the surface and in early endosomes. We also determine that the HSV-1 US3 protein, the shorter US3.5 kinase and the full-length HSV-2 homolog, all predominantly target mature surface rather than total MR1 levels. We propose that the downregulation of intracellular and cell surface MR1 molecules by US3 and other HSV proteins is an immune-evasive countermeasure to minimise the effect of impaired MR1 endocytosis, which might otherwise render infected cells susceptible to MR1-mediated killing by MAIT cells.

Keywords: HSV; MR1; herpesvirus; immunosuppression; receptor endocytosis; viral immunology

DOI: https://doi.org/10.1016/j.jbc.2024.107748

Cell Rep. 2024 Sep 10. pii: S2211-1247(24)01056-8. [Epub ahead of print]43(9): 114705

Unraveling the phenotypic states of human innate-like T cells: Comparative insights with conventional T cells and mouse models.

Liyen Loh, Salomé Carcy, Harsha S Krovi, Joanne Domenico, Andrea Spengler, Yong Lin, Joshua Torres, Rishvanth K Prabakar, William Palmer, Paul J Norman, Matthew Stone, Tonya Brunetti, Hannah V Meyer, Laurent Gapin.

The "innate-like" T cell compartment, known as Tinn, represents a diverse group of T cells that straddle the boundary between innate and adaptive immunity. We explore the transcriptional landscape of Tinn compared to conventional T cells (Tconv) in the human thymus and blood using single-cell RNA sequencing (scRNA-seq) and flow cytometry. In human blood, the majority of Tinn cells share an effector program driven by specific transcription factors, distinct from those governing Tconv cells. Conversely, only a fraction of thymic Tinn cells displays an effector phenotype, while others share transcriptional features with developing Tconv cells, indicating potential divergent developmental pathways. Unlike the mouse, human Tinn cells do not differentiate into multiple effector subsets but develop a mixed type 1/type 17 effector potential. Cross-species analysis uncovers species-specific distinctions, including the absence of type 2 Tinn cells in humans, which implies distinct immune regulatory mechanisms across species.

Keywords: CP: Immunology; MAIT; T cell development; gamma delta T cells; iNKT; thymus

DOI: https://doi.org/10.1016/j.celrep.2024.114705