Biology subjects

Klenerman, P.

Publications and source records attributed to Klenerman, P..

At least 19 recordsLinked to original sources

bioRxiv2026

CXCR3 on transferred T cells enables vaccine-boosted adoptive T-cell therapy in solid tumors

Adoptive T-cell therapy (ACT) has demonstrated marked clinical benefit in hematological malignancies but has limited efficacy against solid tumors. Cancer vaccines can improve ACT, but the mechanisms underlying this combination are poorly understood. Here, we combined ACT with chimpanzee adenovirus ChAdOx1 (ChAd) and modified vaccinia Ankara (MVA) encoding tumor antigens. Whereas PD1 blockade failed to improve ACT, the combination with ChAd/MVA vaccination drove durable regression of established tumors, correlating with expansion of tumor-reactive T cells in lymphoid organs and increased tumor infiltration by T cells. Mechanistically, ChAd priming induced CXCR3 ligands (CXCL10 and CXCL9) in the vaccine-draining lymph node, thereby recruiting transferred T cells to this node independently of cognate antigen. CXCR3 expression on the transferred T cells, but not on host cells, was required for the anti-tumor effect of the combination therapy and favored T-cell accumulation in the vaccine-draining lymph node and the tumor. These findings identify CXCR3 on the transferred T cells as a determinant of ACT plus vaccination synergy and provide a rationale for combining viral-vector vaccines with TCR-T therapies, and for selecting or engineering T cells to retain CXCR3 expression.

immunology↗

bioRxiv2026

Gut archaea drive human MAIT cell responses

Archaea, the third domain of life, are a gut microbiome constituent, but their role in shaping immunity is poorly understood. Mucosal-associated invariant T (MAIT) cells sense microbial metabolites through their T cell receptor and contribute to antimicrobial defence and barrier homeostasis. Key sources of the major MAIT cell antigen 5-OP-RU within the human gut microbiome are unknown. Analysing microbiomes from UK, Zambian, Kenyan and Ugandan donors, we found strong correlations between archaeal riboflavin biosynthesis and circulating MAIT cell frequency and activation. Stool 5-OP-RU levels correlated with archaeal abundance. Cultures of methanogenic archaea, including the human commensal Methanobrevibacter smithii, produced 5-OP-RU and strongly activated MAIT cells without inflammation. We demonstrate a critical role for archaea in shaping human immunity, with implications for microbiome-mediated regulation of health.

immunology↗

bioRxiv2026

Treatment of murine autoimmune myocarditis with a novel monoclonal antibody that targets multiple inflammatory pathways

Severe forms of inflammation-induced acute and chronic myocarditis have a poor prognosis. Promising therapeutic efforts focused on monoclonal antibodies (mAbs) inhibiting inflammation-inducing molecules. However, most mAbs target only one or a limited number of such molecules. Since inflammation involves multiple redundant pathways, we postulated that an mAb inhibiting multiple inflammatory pathways would be a potent therapeutic agent. We initially tested the commercially available anti-natural killer (NK) cell mAb (anti-NK1.1), which binds a receptor expressed on NK cells and depletes them. Since NK cells are key cellular orchestrators of inflammation, by reducing their number, we aimed to inhibit multiple inflammatory pathways. Our initial studies demonstrated that administration of this antibody significantly improved myocardial outcomes in mouse models of acute myocardial infarction and of heart failure. Since NK1.1 is not expressed in human cells, we built on these promising preclinical results by developing a novel mAb targeting CD160 on human NK cells for evaluation as an immunosuppressive therapy. We found that the anti-CD160 mAb depletes both murine and human NK cells. We also found that, while CD160+ cells were largely present in the NK population, they also occurred among CD8+ and {gamma}/{delta} T cell subsets in human cells. Anti-CD160 therapy entirely prevented the deterioration of the myocardial function of mice with autoimmune-induced acute myocarditis. This outcome suggests our novel approach for inhibiting multiple inflammatory pathways may provide a potent strategy for improving outcomes of inflammation-driven myocarditis, as well as of other inflammation-driven diseases. Key PointsO_ST_ABSQuestionC_ST_ABSCan the depletion of CD160+ cells prevent autoimmune-induced myocarditis? FindingsIn this study we found that CD160 is expressed by mouse and human natural killer cells and other subtypes of cytotoxic T cells, and that a monoclonal antibody targeting CD160 depletes NK cells. In a preclinical model of experimental autoimmune myocarditis, administration of the anti-CD160 monoclonal antibody prevented myocardial dysfunction and systemic inflammation. MeaningOur results are compatible with the hypothesis that early autoimmune-induced myocardial dysfunction is promoted by CD160+ cells, which elevate inflammation-induced circulating factors (or factors released by tissue-resident cytotoxic immune cells) that cause myocardial dysfunction in the absence of myocardial necrosis or fibrosis, and further, that targeting CD160+cells with a mAb that depletes NK cells (and probably CD160 expressing cytotoxic T cells) entirely prevents the deterioration of myocardial function in such mice. This outcome suggests our novel approach for inhibiting multiple inflammatory pathways may provide a potent strategy for improving outcomes of inflammation-driven myocarditis, as well as of other inflammation-driven diseases.

systems biology↗

bioRxiv2026

MAIT cells derived ligands signal via VEGFR2 to promote tissue repair and liver regeneration

MAIT are a highly versatile population of innate-like T cells that have been implicated in promoting tissue repair-associated process in a variety of tissue and diseases settings in the last years. While certain specific effector molecules responsible for MAIT-cell mediated have been identified, the mechanisms by which MAIT cells exert repair functions remain incompletely understood. Here, we show that hepatic MAIT cells express VEGFA, VEGFB and vimentin, an alternative ligand for the VEGFA-receptor VEGFR2 in both, regenerating and heathy tissue. Expression and secretion of these factors were induced in vitro by combined T cell receptor and cytokine stimulation. Supernatants of activated MAIT cells were able to promote proliferation of different epithelial and endothelial cells, including a liver sinusoidal endothelial-derived cell line in an VEGFR2-dependent manner. Together, our findings expand our understanding of MAIT cell function, especially in the liver and open new opens avenues for exploring MAIT therapeutic potential in modulating tissue repair.

immunology↗

bioRxiv2025

Single-cell profiling of blood and cerebrospinal fluid in tuberculous meningitis

Tuberculous meningitis (TBM) is the most severe form of tuberculosis, with a fatality rate of 20-50% in treated individuals. Although corticosteroid therapy can increase survival in HIV-negative people with TBM, better antimicrobial and host-directed therapies are required to improve outcome. There is, therefore, a need to better understand local immunopathologic pathways. Despite its power in identifying disease-specific cellular profiles, single-cell RNA-sequencing (scRNA-seq) has been underutilized in cerebral samples in brain infection. We employed scRNA-seq to analyze fresh pretreatment cerebrospinal fluid (CSF) from four TBM patients, along with paired peripheral blood mononuclear cells (PBMCs). While 29 cell subtypes were present in both tissues, their relative abundance varied significantly. In particular, CSF was enriched with highly inflammatory microglia-like macrophages, GZMK-expressing CD8+ T cells, and CD56bright NK cells. The latter two subsets exhibited features associated with dysfunctional cytotoxicity. Across multiple cell types, inflammatory signaling pathways were increased and oxidative phosphorylation was decreased in CSF compared to PBMCs. This study highlights the value of scRNA-seq for exploring CSF immunopathogenesis in TBM patients and offers a resource for future studies investigating the pathophysiology of TBM and other brain infections, including potentially targetable cell populations linked with immune-mediated pathology.

immunology↗

bioRxiv2024

Lineage-aware evolutionary analysis of hepatitis C virus within-host dynamics

Analysis of viral genetic data has previously revealed distinct within-host population structures in both untreated and interferon-treated chronic hepatitis C virus (HCV) infections. While multiple subpopulations persisted during the infection, each subpopulation was observed only intermittently. However, it was unknown whether similar patterns were also present after Direct Acting Antiviral (DAA) treatment, where viral populations were often assumed to go through narrow bottlenecks. Here we tested for the maintenance of population structure after DAA treatment failure. We analysed whole-genome next-generation sequencing data generated from a randomised study using DAAs (the BOSON study). We focused on samples collected from patients (N=84) who did not achieve sustained virological response (i.e. treatment failure) and had sequenced virus from multiple timepoints. For each individual, we tracked concordance in nucleotide variant frequencies through time. Using a sliding window approach, we applied sequenced-based and tree-based clustering algorithms across the entire HCV genome. Finally, we reconstructed viral haplotypes and estimated lineage specific within-host divergence rates from the haplotype phylogenies. Distinct viral subpopulations were maintained among a high proportion of individuals post DAA treatment failure. Using maximum likelihood modelling and model comparison, we found an overdispersion of viral evolutionary rates among individuals, and significant differences in evolutionary rates between lineages within individuals. These results suggest the virus is compartmentalised within individuals, with the varying evolutionary rates due to different viral replication rates or different selection pressures. We propose lineage awareness in future analyses of HCV evolution and infections to avoid conflating patterns from distinct lineages, and to recognise the likely existence of unsampled subpopulations.

evolutionary biology↗

bioRxiv2024

Human tonsil organoids reveal innate pathways modulating humoral and cellular responses to ChAdOx1

The COVID-19 pandemic response demonstrated the effectiveness of adenovirus vector vaccines in inducing protective cellular and antibody responses. However, we still lack mechanistic understanding of the factors regulating immunity induced by this platform, especially innate pathways. We utilized a human tonsil organoid model to study the regulation of adaptive responses to ChAdOx1 nCoV-19. Innate activation and cytokine release occurred within 24 hours and T and B cell activation and antigen-specific antibody secretion occurred during the ensuing 14-day culture. Among the immune cell populations, plasmacytoid dendritic cells (pDCs) exhibited the highest ChAdOx1 transduction levels. pDC-derived IFN- was critical for humoral responses, but production of antigen in pDCs was dispensable. Furthermore, IL-6 enhanced humoral responses in both IFN--dependent and independent manners, indicating intricate signaling interplay. IFN- and IL-6 also regulated the function of vaccine-activated CD4+ T cells, including TFH. These data provide key insights into innate pathways regulating ChAdOx1-induced immunity and highlights the promise of this model for vaccine platform mechanistic studies. SUMMARYDespite the success of adenovirus vector vaccines, we still lack understanding of the mechanisms regulating immunity induced by this platform. This study utilized human tonsil organoids to provide key insights into innate pathways regulating ChAdOx1-induced humoral and cellular immunity.

immunology↗

bioRxiv2024

Early NK-cell and T-cell dysfunction marks progression to severe dengue in patients with obesity and healthy weight

Dengue is a mosquito-borne virus infection affecting half of the worlds population for which therapies are lacking. The role of T and NK-cells in protection/immunopathogenesis remains unclear for dengue. We performed a longitudinal phenotypic, functional and transcriptional analyses of T and NK-cells in 124 dengue patients using flow cytometry and single-cell RNA-sequencing. We show that T/NK-cell signatures early in infection discriminate patients who will progress to severe dengue (SD) from those who do not. In patients with overweight/obesity these signatures are exacerbated compared to healthy weight patients, supporting their increased susceptibility to SD. In SD, CD4+/CD8+ T-cells and NK-cells display increased co-inhibitory receptor expression and decreased cytotoxic capacity compared to non-SD. Furthermore, type-I Interferon signalling is downregulated in SD, suggesting defective virus-sensing mechanisms may underlie NK/T-cell dysfunction. We propose that dysfunctional "professional killer" T/NK-cells underpin dengue pathogenesis. Our findings pave the way for the evaluation of immunomodulatory therapies for dengue.

immunology↗

bioRxiv2024

Neurodegenerative fluid biomarkers are enriched in human cervical lymph nodes

In animal models, brain neurodegeneration biomarkers drain into cervical lymph nodes (CLNs). If this occurred in humans, CLNs may provide a readily accessible source of these biomarkers, draining the site of primary pathology. We tested this hypothesis in discovery and validation cohorts using ultrasound-guided fine needle aspiration (FNA). We measured amyloid-beta 40 and 42, phospho-Tau-181, glial-fibrillary-acidic-protein, and neurofilament-light using single molecule array in CLN aspirates and plasma from: i) a discovery cohort of 25 autoimmune patients, and from ii) plasma, CLNs and capillary blood in four healthy volunteers, an optimisation-validation cohort. FNA was well-tolerated by all participants. In both cohorts, all biomarkers were detected in all plasmas and CLNs, other than neurofilament-light (8/17 of discovery cohort). CLN biomarker concentrations were significantly greater than plasma concentrations for all except neurofilament-light, most markedly for phospho-Tau-181 (266 fold; P<0.02), whose CLN concentrations decreased with age (Spearman r=-0.66, P=0.001). This study presents the first evidence that neurodegenerative biomarkers are detectable in human CLNs. Raised CLN:plasma biomarker ratios suggest their concentration in CLNs, which may offer a sensitive compartment for minimally-invasive sampling in clinical trials. Further, age-associated phospho-Tau-181 reduction with age suggests FNA of CLNs may measure the integrity of brain lymphatic drainage in vivo.

neuroscience↗

bioRxiv2024

MAIT cells protect against sterile lung injury

Mucosal-associated invariant T (MAIT) cells, the most abundant unconventional T cells in the lung, have been recently linked to tissue protection and repair. Their role, especially in sterile lung injury, is unknown. Using single cell RNA sequencing (scRNA-seq), spectral analysis and adoptive transfer in a bleomycin-induced sterile lung injury, we found that bleomycin activates murine pulmonary MAIT cells and induces an accompanying tissue repair programme, associated with a protective role against bleomycin-induced lung injury. MAIT cells drive the accumulation of type 1 conventional dendritic cells (cDC1), limiting tissue damage in a DNGR-1 dependent manner. Human scRNA-seq data revealed that MAIT cells were activated, with increased cDC populations in idiopathic pulmonary fibrosis patients. Thus, MAIT cells enhance defence against sterile lung injury by fostering cDC1-driven anti-fibrotic pathways.

immunology↗

bioRxiv2023

Fine needle aspiration of human lymph nodes reveals cell populations and soluble interactors pivotal to immunological priming

Lymph node (LN) fine needle aspiration (LN FNA) represents a powerful technique for minimally invasive sampling of human lymph nodes in vivo and has been used to good effect to directly study aspects of the human germinal center response. However, systematic deep phenotyping of the cellular populations and cell-free proteins recovered by LN FNA has not been performed. Thus, we studied human cervical LN FNAs as a proof-of-concept and used single-cell RNA-sequencing and proteomic analysis to benchmark this compartment, define the purity of LN FNA material, and facilitate future studies into this immunologically pivotal environment. Our data provide evidence that LN FNAs contain bone fide LN-resident innate immune populations, with minimal contamination of cells or proteins from blood. Examination of these populations reveals unique biology not predictable from equivalent blood-derived populations. LN FNA supernatants represent a specific source of lymph- and lymph node-derived proteins, and can, in combination with transcriptomic approaches, identify likely receptor-ligand interactions. This study provides the first description of the types and abundance of immune cell populations and cell-free proteins that can be efficiently studied by LN FNA. These findings are of broad utility for understanding LN physiology both in health and disease, including infectious or autoimmune perturbations, and in the case of cervical nodes, neuroscience.

immunology↗

bioRxiv2023

Gonadal androgens are associated with decreased type I interferon production by pDCs and increased IgG titres to BNT162b2 following co-vaccination with live attenuated influenza vaccine in adolescents

mRNA vaccine technologies introduced following the SARS-CoV-2 pandemic have highlighted the need to better understand the interaction of adjuvants and the early innate immune response. Interferon type I (IFN-I) is an integral part of this early innate response and can prime several components of the adaptive immune response. Females are widely reported to respond better than males to seasonal tri- and quad-valent influenza vaccines. Plasmacytoid dendritic cells (pDCs) are the primary cell type responsible for IFN-I production and female pDCs produce more IFN-I than male pDCs since the upstream receptor TLR7 is encoded by the X-chromosome and is biallelically expressed by up to 30% of female immune cells. Additionally, the TLR7 promoter contains putative androgen response elements and androgens have been reported to suppress pDC IFN-I in-vitro. Unexpectedly, therefore, we recently observed that male adolescents mount stronger antibody responses to the Pfizer BNT162b2 mRNA vaccine than female adolescents after controlling for natural SARS-CoV-2 infection. We here examined pDC behaviour in this cohort to determine the impact of IFN-I on anti-Spike and anti-receptor-binding domain titres to BNT162b2. Through LASSO modelling we determined that serum free testosterone was associated with reduced pDC IFN-I but, contrary to the well-described immunosuppressive role for androgens, the more potent androgen dihydrotestosterone was associated with increased IgG titres to BNT162b2. Also unexpectedly, we observed that co-vaccination with live-attenuated influenza vaccine boosted the magnitude of IgG responses to BNT162b2. Together these data support a model where systemic IFN-I increased vaccine-mediated immune responses, but for vaccines with intracellular stages, modulation of the local IFN-I response may alter antigen longevity and consequently vaccine-driven immunity. Author SummaryType I interferons (IFN-I) are potent antiviral proteins which play a central role in activating the immune response and driving inflammation. IFN-I is predominantly produced by plasmacytoid dendritic cells (pDCs) and female pDCs produce more IFN-I than male pDCs. Consequently, females typically generate stronger antibody responses to vaccines such as seasonal influenza vaccines. In addition, females typically suffer more serious adverse events from vaccines. However, we recently reported in a study of adolescents that males generate stronger antibody responses to the SARS-CoV-2 mRNA vaccine BNT162b2 than females. Here we examine the IFN-I response of pDCs in adolescents co-/vaccinated with BNT162b2 and live-attenuated influenza vaccine (LAIV). We find that male sex hormones reduce pDC IFN-I but are associated with increased BNT162b2 antibody titres. We also observe that LAIV boosts BNT162b2 antibody titres through possible bystander activation of immune cells. These findings are consistent with a reportedly higher incidence of adverse events among males associated with this vaccine. Together these data suggest that IFN-I production typically enhances vaccine-specific immune responses but for new mRNA vaccines such as BNT162b2, that are modified to reduce innate immunogenicity, localised dampening of the IFN-I response in vaccinated tissue by male sex hormones may further delay the clearance of the vaccine, increasing vaccine antigen exposure and allowing time for a stronger antibody response.

immunology↗

bioRxiv2023

Primed to resolve: A single cell atlas of the shoulder capsule reveals a cellular basis for resolving inflammatory fibrosis

Fibrotic conditions are a significant global disease burden. While some therapies delay disease progression, none reverse fibrosis. To gain insights into how fibrosis might resolve, we developed a comparative single cell atlas of frozen shoulder capsule tissue; a chronic inflammatory fibrotic human disease that resolves spontaneously. We identified both a population of pro-inflammatory MERTKlowCD48+ macrophages (M{varphi}) and a population of MERTK+LYVE1+MRC1+M{varphi} enriched for negative regulators of inflammation. Micro-cultures of patient-derived cells identified cell-matrix interactions between MERTK+M{varphi} and DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in the resolution of frozen shoulder. Cross-tissue analysis revealed a shared gene expression cassette between MERTK+M{varphi} in the shoulder capsule and a similar cell population enriched in synovial tissues from rheumatoid arthritis patients in disease remi ssion, supporting the concept that MERTK+M{varphi} provide a cellular basis for the resolution of inflammation and fibrosis. Single-cell transcriptomic profiling and spatial analysis of human foetal shoulder tissues identified MERTK+LYVE1+MRC1+M{varphi} and DKK3+ and POSTN+ fibroblast populations analogous to those identified in adult shoulder capsule, suggesting that the template to resolve fibrosis is established during development. Therapeutic enhancement of crosstalk between MerTK+M{varphi} and pro-resolving DKK3+ and POSTN+ fibroblasts could accelerate resolution of frozen shoulder and resolve persistent inflammatory fibrotic disease in other tissues.

cell biology↗

bioRxiv2022

A conserved population of MHC II-restricted, innate-like, commensal-reactive T cells in the gut of humans and mice

Interactions with commensal microbes shape host immunity on multiple levels and are recognized to play a pivotal role in human health and disease. In this study, we show that MHC-II restricted, commensal-reactive T cells in the colon of both humans and mice acquire transcriptional and functional characteristics typically associated with innate-like T cells, including the expression of the key transcription factor PLZF and the ability to respond to cytokines including IL-12, IL-18 and IL-23 in a TCR-independent manner. These MHC-II restricted, innate-like, commensal-reactive T cells (TMIC) are endowed with a polyfunctional effector potential spanning classic Th1- and Th17-cytokines, cytotoxic molecules as well as regulators of epithelial homeostasis and represent an abundant and conserved cell population in the human and murine colon. T cells with the TMIC phenotype were increased in ulcerative colitis patients and their presence aggravated pathology in DSS-treated mice, pointing towards a pathogenic role in colitis. Our findings add TMIC cells to the expanding spectrum of innate-like immune cells positioned at the frontline of intestinal immune surveillance, capable of acting as sentinels of microbes and the local cytokine milieu.

immunology↗

bioRxiv2022

MR1 dependent MAIT cell activation is regulated by autophagy associated proteins

The antigen presenting molecule, MR1, presents microbial metabolites to MAIT cells, a population of innate-like, anti-microbial T cells. It also presents an unidentified ligand to MR-1 restricted T cells in the setting of cancer. The cellular co-factors that regulate MR1 antigen presentation have yet to be fully defined. We performed a mass spectrometry-based proteomics screen to identify MR1 interacting proteins and discovered the selective autophagy receptor SQSTM1/p62. CRISPR-Cas9-mediated knock out of SQSTM1/p62 increased MAIT cell activation in the presence of E.coli but not the synthetic ligand 5-OP-RU whereas depletion of Atg5 and Atg7, key autophagy proteins, increased MAIT activation irrespective of the ligand used. This regulation appears to occur at an early step in the MR1 trafficking pathway. This data implicates distinct roles for autophagy associated proteins in the regulation of MR1 activity and highlights the contribution of the autophagy pathway to regulation of cellular antigen presentation.

cell biology↗

bioRxiv2022

Genome-first detection of emerging resistance to novel therapeutic agents for SARS-CoV-2

Some COVID-19 patients are unable to clear their infection or are at risk of severe disease, requiring treatment with neutralising monoclonal antibodies (nmAb) and/or antivirals. The rapid roll-out of novel therapeutics means there is limited understanding of the likely genetic barrier to drug resistance. Unprecedented genomic surveillance of SARS-CoV-2 in the UK has enabled a genome-first approach to the detection of emerging drug resistance. Here we report the accrual of mutations in Delta and Omicron cases treated with casirivimab+imdevimab and sotrovimab respectively. Mutations occur within the epitopes of the respective nmAbs. For casirivimab+imdevimab these are present on contiguous raw reads, simultaneously affecting both components. Using surface plasmon resonance and pseudoviral neutralisation assays we demonstrate these mutations reduce or completely abrogate antibody affinity and neutralising activity, suggesting they are driven by immune evasion. In addition, we show that some mutations also reduce the neutralising activity of vaccine-induced serum.

genetics↗

bioRxiv2022

Further antibody escape by Omicron BA.4 and BA.5 from vaccine and BA.1 serum

The Omicron lineage of SARS-CoV-2, first described in November 2021, spread rapidly to become globally dominant and has split into a number of sub-lineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africas Gauteng region uncovered two new sub-lineages, BA.4 and BA.5 which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences and, although closely related to BA.2, contain further mutations in the receptor binding domain of spike. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by serum from triple AstraZeneca or Pfizer vaccinated individuals compared to BA.1 and BA.2. Furthermore, using serum from BA.1 vaccine breakthrough infections there are likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.

microbiology↗

bioRxiv2022

Human MAIT cells show clonal diversity but transcriptional and functional homogeneity

Mucosal-associated invariant T (MAIT) cells are considered to have limited clonal diversity. In contrast, recent studies suggest the presence of functionally distinct subsets. We investigated this model through single-cell analysis of the MAIT cell TCR repertoire and transcriptional profile in human blood and liver. Further, we developed functional RNA-sequencing (fRNA-seq), an approach to integrate cellular function and TCR clonotype at a single-cell level following differential stimulation. MAIT cells showed surprising clonal diversity, with TCR repertoires shared across tissues but unique to individuals. Functional diversity within resting MAIT cells was low and largely related to tissue site. MAIT cells displayed distinct transcriptional responses to in vitro TCR and cytokine stimulation, with cells positioned along gradients of activation. Clonal origin influenced both resting and activated transcriptional profiles. Overall, MAIT cells exhibit diverse donor-specific TCR repertoires which, along with tissue and activation context, influence their phenotype and function.

immunology↗