A5071766732- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Influenza Virus Research Studies
- interferon and immune responses
- Respiratory viral infections research
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Diabetes and associated disorders
- Animal Disease Management and Epidemiology
- Epigenetics and DNA Methylation
- Animal Virus Infections Studies
- Virology and Viral Diseases
- Cytomegalovirus and herpesvirus research
- Cancer Immunotherapy and Biomarkers
- Viral Infectious Diseases and Gene Expression in Insects
- Viral Infections and Immunology Research
- Biosimilars and Bioanalytical Methods
- Pneumonia and Respiratory Infections
- Viral Infections and Vectors
- Immune cells in cancer
- Hematopoietic Stem Cell Transplantation
- Vector-Borne Animal Diseases
Lentigen Technology (United States)
2022-2024
St. Jude Children's Research Hospital
2011-2020
Center for Infectious Disease Research
2013
Cold Spring Harbor Laboratory
2012
Howard Hughes Medical Institute
2012
Johns Hopkins University
2012
The Pirbright Institute
2005-2010
The ability to decode antigen specificities encapsulated in the sequences of rearranged T-cell receptor (TCR) genes is critical for our understanding adaptive immune system and promises significant advances field translational medicine. Recent developments high-throughput sequencing methods (immune repertoire technology, or RepSeq) single-cell RNA technology have allowed us obtain huge numbers TCR from donor samples link them phenotypes. However, annotate these still lags behind, owing...
CD8 + T cell diversity may be more important than abundance in limiting the negative consequences of cytomegalovirus persistence.
Characterizing the TCRα and TCRβ chains expressed by T cells responding to a given pathogen or underlying autoimmunity helps in development of vaccines immunotherapies, respectively. However, our understanding complementary chain utilization is very limited for pathogen- autoantigen-induced immunity. To address this problem, we have developed multiplex nested RT-PCR method simultaneous amplification transcripts encoding from single cells. This circumvented lack antibodies specific variable...
Studies on mucosal-associated invariant T cells (MAITs) in nonhuman primates (NHP), a physiologically relevant model of human immunity, are handicapped due to lack macaque MAIT-specific reagents. Here we show that while MR1 ligand-contact residues conserved between and multiple NHP species, three T-cell receptor contact-residue mutations diminish binding tetramers MAITs. Construction naturally loaded facilitated identification characterization MR1-binding ligands MAITs, both which mirrored...
It is currently thought that T cells with specificity for self-peptide/MHC (pMHC) ligands are deleted during thymic development, thereby preventing autoimmunity. In the case of CD4 + cells, what unclear extent to which class II (pMHCII)-specific or become Foxp3 regulatory cells. We addressed this issue by characterizing a natural polyclonal pMHCII-specific T-cell population in mice either lacked expressed relevant antigen ubiquitous pattern. Mice expressing contained one-third number as...
Development of αβ and γδ T cells requires coupling environmental signals with metabolic redox regulation by mTORC1.
CAR T-cell therapies targeting the B-cell maturation antigen eliminate tumors in relapsed/refractory multiple myeloma patients, however durable remissions remain difficult to attain. Transforming growth factor beta (TGF-β) is a multifunctional cytokine abundantly expressed bone marrow niche, where it promotes an immunosuppressive tumor microenvironment. We hypothesized that BCMA T-cells armored resist suppressive effects of TGF-β will provide advantage treating myeloma. The B2ARM T cells,...
Background Chimeric antigen receptor (CAR) T-cell therapy target tyrosine kinase-like orphan 1 (ROR1) is broadly expressed in hematologic and solid tumors, however clinically-characterized ROR1-CAR T cells with single chain variable fragment (scFv)-R12 targeting domain failed to induce durable remissions, part due the immunosuppressive tumor microenvironment (TME). Herein, we describe development of an improved a novel, fully human scFv9 domain, augmented TGFβRIIDN armor protective against...
Following respiratory syncytial virus infection of adult CB6F1 hybrid mice, a predictable CD8+ T cell epitope hierarchy is established with strongly dominant response to K(d)-restricted peptide (SYIGSINNI) from the M2 protein. The K(d)M2(82-90) ∼5-fold higher than subdominant M protein (NAITNAKII, D(b)M(187-195)). After neonatal distinctly different emerges codominant responses and D(b)M(187-195). Adoptive transfer naïve cells adults into congenic neonates prior indicates that intrinsic...
Transgenic expression of antigen-specific T-cell receptor (TCR) genes is a promising approach for immunotherapy against infectious diseases and cancers. A key to the efficient application this rapid specific isolation cloning TCRs. Current methods are often labor-intensive, nonspecific, and/or relatively slow. Here, we describe an system αβTCR CDR3 substitution. We demonstrate capability influenza-specific TCRs within 10 days using single-cell polymerase chain reaction (PCR) Gibson Assembly...
T cells are classically recognized as distinct subsets that express αβ or γδ TCRs. We identify a novel population of coexpress and TCRs in mice humans. These hybrid αβ-γδ arose the murine fetal thymus by day 16 ontogeny, underwent TCR–mediated positive selection into CD4+ CD8+ thymocytes, constituted up to 10% TCRδ+ lymphoid organs. They expressed high levels IL-1R1 IL-23R secreted IFN-γ, IL-17, GM-CSF response canonically restricted peptide antigens stimulation with IL-1β IL-23. Hybrid were...
The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and to investigate host-pathogen interactions at a systems level. This generated 47 transcriptomic proteomic datasets from 30 studies that in vivo vitro host responses viral infections. Human pathogens Orthomyxoviridae Coronaviridae families, especially pandemic H1N1 avian H5N1 influenza A viruses severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated....
Although γδ T cells comprise up to 10% of human peripheral blood cells, questions remain regarding their role in disease states and T-cell receptor (TCR) clonal expansions. We dissected anti-viral functions towards influenza viruses defined influenza-reactive TCRs the context γδ-TCRs across lifespan.We performed 51Cr-killing assay single-cell time-lapse live video microscopy define mechanisms underlying T-cell-mediated killing influenza-infected targets. assessed cytotoxic profiles patients...
Type I alveolar epithelial cells are a replicative niche for influenza in vivo, yet their response to infection is not fully understood. To better characterize cellular responses, we have created an immortalized murine lung type cell line (LET1). These support spreading virus the absence of exogenous protease and thus permit simultaneous analysis viral replication dynamics host responses. LET1 can be productively infected with human, swine mouse-adapted strains exhibit expression antiviral...
T‐cell receptor (TCR) usage has an important role in determining the outcome of CD8 + cytotoxic T‐lymphocyte responses to viruses and other pathogens. However, characterization TCR from which such conclusions are drawn is based on exclusive analysis either TCRα chain or, more commonly, TCRβ chain. Here, we have used a multiplexed reverse transcription‐PCR protocol analyse CDR3 regions both β chains single naive or immune epitope‐specific cells provide comprehensive picture selection into...