Leland Stanford Junior University

Other

Mark M Davis

Chang-Zheng Chen

Jacqueline Chau

Qi-Jing Li

Stephen M Hedrick

Ronald W Davis

Michael Nicholas Mindrinos

Sujatha Krishnakumar

Naresha Saligrama

Chunlin Wang

Thomas J Schall

Eric Andrew Appel

Jacob Glanville

Howard Y Chang

Daniel Lewis Kraft

Patrick O Brown

Joseph C Wu

Alan M Krensky

Atul J Butte

Shai S Shen-Orr

Daniel Shin-Yu Chen

Santiago Correa

Yu Wong

Qian Yin

Arnold Han

Jeremy Pearl

Yoav Soen

David Furman

Peter S Lu

Brian A Kidd

Jan Jongstra

John D Altman

Michael G McHeyzer-Williams

Gillie A Roth

Emily C Gale

Ansuman Satpathy

Provided herein are methods and compositions for diagnosis and treatment of multiple sclerosis. Compositions and methods are provided, relating to novel peptides involved in autoimmune disease. In the experiments described herein, an unbiased approach was used to screen pathogenic CD4+ T cells from patients with multiple sclerosis (MS), and to determine the antigenic specificity of the T cell receptors (TCR) expressed by these pathogenic cells.

Cross-reactive epitope for multiple sclerosis

An immunomodulatory delivery system includes a hydrogel, a first immunomodulatory cargo encapsulated in the cargo, and a second immunomodulatory cargo encapsulated in the hydrogel. The hydrogel includes a polymer non-covalently crossed-linked with a plurality of nanoparticles. The first immunomodulatory cargo is smaller than the second immunomodulatory cargo. A ratio of a diffusivity of the first immunomodulatory cargo through the hydrogel to a diffusivity of the second immunomodulatory cargo through the hydrogel is less than 3.

Injectable hydrogels for controlled release of immunomodulatory compounds

Provided are systems and methods that can combine T cell receptor sequencing (TCRseq) and Assay for Transposase Accessible Chromatin using sequencing (ATAC-seq), and/or respective aspects thereof. Further provided are systems and methods that can combine ATAC-seq and perturbation sequencing (Perturb-seq), and/or respective aspects thereof.

Systems and methods for multiplexed measurements in single and ensemble cells

Polymeric nanoparticles comprising a defined set of biologically active agents that provide for targeted stimulation of non-responsive T cells, e.g. T cells involved in cancer, are provided.

Polymeric nanoparticles for enhanced cancer immunotherapy

Methods and oligonucleotide reagents for analyzing individual T cells are disclosed. In particular, the present disclosure provides methods for analyzing individual T cells using high-throughput multiplex amplification and deep sequencing of nucleic acids encoding T cell receptors (TCRs) and various other T cell phenotypic markers. The present disclosure further provides methods of reconstituting TCRs from individual T cells for functional studies, ligand discovery, or screening therapeutics.

Single cell analysis of T cells using high-throughput multiplex amplification and deep sequencing

Embodiments of the present invention provide diagnostic markers of immunosenescence and methods of identifying individuals with impaired immune function based on a combination of such markers obtained from various analyzes, primarily from blood, testing immune function including the analysis of immune cell subset frequencies, gene expression, cytokine and chemokine levels, and signaling responses to stimulation with cytokines ('cytokine response'). Particular combinations of markers can predict with high accuracy whether an individual will respond to active vaccination and become protected against recurring diseases.

Method of assaying an individual for immune impairment

Methods are provided to determine the entire genomic region of a particular HLA locus including both intron and exons. The resultant consensus sequences provides linkage information between different exons, and produces the unique sequence from each of the two genes from the individual sample being typed. The sequence information in intron regions along with the exon sequences provides an accurate HLA haplotype.

Haplotying of HLA loci with ultra-deep shotgun sequencing

MicroRNAs (miRNAs) are a diverse and abundant class of &#x2dc;22-nucleotide (nt) endogenous regulatory RNAs that play a variety of roles in animal cells by controlling gene expression at the posttranscriptional level. Increased miR-181a expression in mature T cells is shown to cause a marked increase in T cell activation and augments T cell sensitivity to peptide antigens. Moreover, T cell blasts with higher miR-181a expression become reactive to antagonists. The effects of miR-181a on antigen discrimination are in part achieved by dampening the expression of multiple negative regulators in the T cell receptor (TCR) signaling pathway, including PTPN22 and the dual specificity phosphatases DUSP5 and DUSP6. This results in a reduction in the TCR signaling threshold, thus quantitatively and qualitatively enhancing T cell sensitDynaivity to antigens.

Modulation of T cell signaling threshold and T cell sensitivity to antigens

Compositions and methods are provided for transplantation of pluripotent stem cells and differentiated cells derived therefrom.

Prevention of immunological rejection of transplanted stem cells by leukocyte costimulatory molecule blockade

MicroRNAs (miRNAs) are a diverse and abundant class of &#x2dc;22-nucleotide (nt) endogenous regulatory RNAs that play a variety of roles in animal cells by controlling gene expression at the posttranscriptional level. Increased miR-181a expression in mature T cells is shown to cause a marked increase in T cell activation and augments T cell sensitivity to peptide antigens. Moreover, T cell blasts with higher miR-181a expression become reactive to antagonists. The effects of miR-181a on antigen discrimination are in part achieved by dampening the expression of multiple negative regulators in the T cell receptor (TCR) signaling pathway, including PTPN22 and the dual specificity phosphatases DUSP5 and DUSP6. This results in a reduction in the TCR signaling threshold, thus quantitatively and qualitatively enhancing T cell sensitivity to antigens.

T cells are profiled with respect to their expression of antigen receptor. The cells are arrayed on a planar or three-dimensional substrate through binding to immobilized or partially diffused MHC-antigen complexes. The cells may further be characterized with respect to their ability to respond to external stimulus in the microenvironment. External stimuli include cell-cell interactions, response to factors, and the like.

MHC-antigen arrays for detection and characterization of immune responses

MicroRNAs (miRNAs) are a diverse and abundant class of &#x2dc;22-nucleotide (nt) endogenous regulatory RNAs that play a variety of roles in animal cells by controlling gene expression at the posttranscriptional level. Increased miR-181expression in mature T cells is shown to cause a marked increase in T cell activation and augments T cell sensitivity to peptide antigens. Moreover, T cell blasts with higher miR-181expression become reactive to antagonists. The effects of miR-181on antigen discrimination are in part achieved by dampening the expression of multiple negative regulators in the T cell receptor (TCR) signaling pathway, including PTPN22 and the dual specificity phosphatases DUSP5 and DUSP6. This results in a reduction in the TCR signaling threshold, thus quantitatively and qualitatively enhancing T cell sensitivity to antigens.

The present invention relates to molecules involved in cell-cell interactions in the immune system. In particular, the invention relates to a cell surface protein which contains certain classical cadherin characteristics, but it exhibits an apical distribution pattern on the surface of lymphocytes. The membrane location of this molecule correlates with the contact interface between T and B cells, and antibodies against an extracellular domain of this protein disrupt T cell/B cell interactions.

Growing community of inventors

Atherton, CA, United States of America

Mark M Davis