A5076452357- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- CAR-T cell therapy research
- Psoriasis: Treatment and Pathogenesis
- Systemic Lupus Erythematosus Research
- Cellular transport and secretion
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- Toxin Mechanisms and Immunotoxins
- Cytomegalovirus and herpesvirus research
- Reproductive System and Pregnancy
- Immune responses and vaccinations
- NF-κB Signaling Pathways
- Hepatitis C virus research
- Ubiquitin and proteasome pathways
- Nicotinic Acetylcholine Receptors Study
- Antimicrobial Peptides and Activities
- Single-cell and spatial transcriptomics
- Mosquito-borne diseases and control
- DNA Repair Mechanisms
- Cytokine Signaling Pathways and Interactions
- Immunodeficiency and Autoimmune Disorders
- Cell death mechanisms and regulation
Amgen (United States)
2020-2024
Memorial Sloan Kettering Cancer Center
2009-2019
Kettering University
2018
National Institute of Immunology
2004-2017
Howard Hughes Medical Institute
2009-2017
University of Washington
2009-2010
Ambedkar University Delhi
2001
University of Delhi
2001
Distinct classes of protective immunity are guided by activation STAT transcription factor family members in response to environmental cues. CD4+ regulatory T cells (T(regs)) suppress excessive immune responses, and their deficiency results a lethal, multi-organ autoimmune syndrome characterized helper 1 (TH1) 2 (TH2) cell-dominated lesions. Here we show that pathogenic TH17 responses mice also restrained T(regs). This suppression was lost upon T(reg)-specific ablation Stat3, critical for...
Abstract Antigen-specific regulatory T cells (Tregs) suppress pathogenic autoreactivity and are potential therapeutic candidates for autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis is associated with to the Smith (Sm) autoantigen human leucocyte antigen (HLA)-DR15 haplotype; hence, we investigated of Sm-specific Tregs (Sm-Tregs) disease. Here identify a HLA-DR15 restricted immunodominant Sm cell epitope using biophysical affinity binding assays, then...
We have recently described two independent mouse models in which the administration of diphtheria toxin (DT) leads to specific depletion regulatory T cells (Tregs) due expression DT receptor-enhanced GFP under control Foxp3 promoter. Both develop severe autoimmune disorders when Foxp3(+) Tregs are depleted. Those findings were challenged a recent study published this journal suggesting epithelial as cause for disease development. By using genetic, cellular, and immunohistochemical...
Generation of cellular heterogeneity is an essential feature the adaptive immune system. This best exemplified during humoral response when expanding B cell clone assumes multiple fates, including class-switched cells, antibody-secreting plasma and memory cells. Although each type for immunity, their generation must be exquisitely controlled because a cannot revert back to parent isotype, terminally differentiated contribute pool. In this study, we show that environmental sensor, aryl...
Abstract The Nef protein of HIV-1 is essential for its pathogenicity and known to down-regulate MHC expression on infected cell surfaces. We now show that also redistributes the costimulatory molecules CD80 CD86 away from surface in human monocytic U937 line as well mouse macrophages dendritic cells. Furthermore, HIV-1-infected cells blood-derived a similar loss CD86. colocalizes with class I (MHCI), CD80, intracellular compartments, binds both Some mutants defective MHCI down-modulation,...
Endocytosis of the nicotinic acetylcholine receptor (AChR) is a proposed major mechanism neuromodulation at neuromuscular junctions and in pathology synapses central nervous system. We show that binding competitive antagonist α-bungarotoxin (αBTX) or antibody-mediated cross-linking induces internalization cell surface AChR to late endosomes when expressed heterologously Chinese hamster ovary cells endogenously C2C12 myocytes. Internalization occurs via sequestration AChR–αBTX complexes...
Among all T and NK cell subsets, regulatory (Treg) cells typically respond to the lowest concentrations of IL-2 due elevated surface expression IL-2R alpha chain (CD25) high affinity receptor (IL-2R) complex. This enhanced sensitivity forms basis for low-dose (LD) therapy treatment inflammatory diseases, where efficacy correlates with increased Treg number functional markers. Despite strong preclinical support this approach, moderate variable clinical has raised concerns that adequate...
Regulatory T (Treg) cells have long been recognized as modulators of immunological tolerance and homeostasis. Previously, we used scRNA-seq to reveal significant Treg heterogeneity in response IL-2-induced activation. Herein, leveraged enrichment analyses, well bulk single nucleus multi-omics splenic lung Tregs, uncover confirm the importance transcription factors (TFs) chromatin remodeling Multiple bZIP TF motifs showed increased accessibility post IL-2 treatment, with correlated...
Antigen-presenting cells (APCs) are expected to present peptides from endocytosed proteins via major histocompatibility complex (MHC) class II (MHCII) molecules T cells. However, a large proportion of purified MHCII derived cytosolic self-proteins making the pathway peptide loading onto critical relevance in regulation immune self-tolerance. We show that cytoplasmic either introduced or expressed cytoplasm first detectable as MHCII-peptide complexes LAMP-1+ lysosomes, prior their delivery...
Mucosal-associated invariant T (MAIT) cells are an abundant class of innate restricted by the MHC I-related molecule MR1. MAIT can recognize bacterially-derived metabolic intermediates from riboflavin pathway presented MR1 and postulated to play a role in antibacterial immunity through production cytokines direct bacterial killing. tetramers, typically stabilized adduct 5-amino-6-D-ribitylaminouracil (5-A-RU) methylglyoxal (MeG), important tools for study cells. A long-standing problem with...
The human immunodeficiency virus type 1 (HIV-1) Vpu accessory protein is a transmembrane that down regulates CD4 expression and promotes the release of new virions. We screened leukocyte-specific yeast two-hybrid library to discover novel Vpu-interacting cellular proteins. major histocompatibility complex class II (MHC II) invariant chain, also called Ii or CD74, was found be one such protein. show direct binding CD74 by using assay coimmunoprecipitation from HIV-1-infected cells....
The Nef protein of HIV-1 mediates immune evasion by relocating major histocompatibility complex (MHC) molecules and the costimulatory CD80 CD86 away from monocytic cell surface. We describe a two-pronged mechanism which removes While MHCI, CD80, are all internalized via dynamin-independent pathway, endocytic used for is distinct MHCI relocation. expression results in activation actin-dependent translocation Src kinase to periphery. At surface, promotes Rac TIAM, guanine nucleotide exchange...
The Nef protein of HIV-1 removes the immune costimulatory proteins CD80 and CD86 from cell surface by a unique clathrin- dynamin-independent, actin-based endocytic pathway that deploys coupled activation c-src Rac. In this study, we show that, similar to major histocompatibility complex class I (MHCI), subsequently reroutes Golgi region. However, not only are CD80/CD86 internalized different mechanism MHCI but also vesicular delivery for is distinct employed MHCI. While passes through early...
Abstract T cell response magnitudes increase with increasing antigenic dosage. However, it is unclear whether ligand density only modulates the proportions of responding ligand-specific cells or also alters responses at single level. Using brief (3 h) exposure TCR-transgenic mouse CD8 in vitro to varying densities cognate peptide-MHC followed by ligand-free culture IL-2, we found that determined frequencies but not expression levels early activation marker molecule, CD69. Cells low glucose...