This study investigated the effects of oil addition on the physical and chemical properties of high-moisture texturized proteins (HMTPs), focusing on soy protein isolate (SPI) and pea protein isolate (PPI). Rheological analysis revealed contrasting behaviors: SPI exhibited decreased rheological parameters at low oil concentrations (1, 3 %), followed by a significant increase at higher concentrations (5, 10 %), whereas PPI showed a consistent decline across all oil concentrations. The superior emulsifying and gelling abilities of SPI resulted in stronger protein-protein interactions and greater hardness at higher oil concentrations.
View Article and Find Full Text PDFSystems vaccinology studies have been used to build computational models that predict individual vaccine responses and identify the factors contributing to differences in outcome. Comparing such models is challenging due to variability in study designs. To address this, we established a community resource to compare models predicting booster responses and generate experimental data for the explicit purpose of model evaluation.
View Article and Find Full Text PDFOutbreaks of (BP), the causative agent of whooping cough, continue despite broad vaccination coverage and have been increasing since vaccination switched from whole-BP (wP) to acellular BP (aP) vaccines. wP vaccination has been associated with more durable protective immunity and an induced Th1 polarized memory T cell response. Here, a multi-omics approach was applied to profile the immune response of 30 wP and 31 aP-primed individuals and identify correlates of T cell polarization before and after Tdap booster vaccination.
View Article and Find Full Text PDFT cells are a critical component of the response to SARS-CoV-2, but their kinetics after infection and vaccination are insufficiently understood. Using "spheromer" peptide-MHC multimer reagents, we analyzed healthy subjects receiving two doses of the Pfizer/BioNTech BNT162b2 vaccine. Vaccination resulted in robust spike-specific T cell responses for the dominant CD4 (HLA-DRB115:01/S191) and CD8 (HLA-A02/S691) T cell epitopes.
View Article and Find Full Text PDFBackground: Allergic disease reflects specific inflammatory processes initiated by interaction between allergen and allergen-specific IgE. Specific immunotherapy (SIT) is an effective long-term treatment option, but the mechanisms by which SIT provides desensitization are not well understood.
Objective: Our aim was to characterize IgE sequences expressed by allergen-specific B cells over a 3-year longitudinal study of patients with aeroallergies who were undergoing SIT.
Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a different strain harboring the spike variant D614G.
View Article and Find Full Text PDFClinical diagnosis typically incorporates physical examination, patient history, and various laboratory tests and imaging studies, but makes limited use of the human system's own record of antigen exposures encoded by receptors on B cells and T cells. We analyzed immune receptor datasets from 593 individuals to develop , an interpretive framework to screen for multiple illnesses simultaneously or precisely test for one condition. This approach detects specific infections, autoimmune disorders, vaccine responses, and disease severity differences.
View Article and Find Full Text PDFPreterm labor (PTL) is the leading cause of neonatal morbidity and mortality worldwide. Whereas many studies have investigated the maternal immune responses that cause PTL, fetal immune cell activation has recently been raised as an important contributor to the pathogenesis of PTL. In this study, we analyzed lymphocyte receptor repertoires in maternal and cord blood from 14 term and 10 preterm deliveries, hypothesizing that the high prevalence of infection in patients with PTL may result in specific changes in the T cell and B cell repertoires.
View Article and Find Full Text PDFVaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode humoral immune memory. We evaluated pediatric and adult blood and deceased adult organ donor tissues to determine convergent antigen-specific antibody genes of similar sequences shared between individuals. B cell memory varied for different pathogens.
View Article and Find Full Text PDFRecovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a new strain harboring the spike variant D614G.
View Article and Find Full Text PDFB cells are critical for the production of antibodies and protective immunity to viruses. Here we show that patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) display early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify convergence of antibody sequences across SARS-CoV-2-infected patients, highlighting stereotyped naive responses to this virus.
View Article and Find Full Text PDFDuring virus infection B cells are critical for the production of antibodies and protective immunity. Establishment of a diverse antibody repertoire occurs by rearrangement of germline DNA at the immunoglobulin heavy and light chain loci to encode the membrane-bound form of antibodies, the B cell antigen receptor. Little is known about the B cells and antigen receptors stimulated by the novel human coronavirus SARS-CoV-2.
View Article and Find Full Text PDFDuring virus infection B cells are critical for the production of antibodies and protective immunity. Here we show that the human B cell compartment in patients with diagnostically confirmed SARS-CoV-2 and clinical COVID-19 is rapidly altered with the early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify extensive convergence of antibody sequences across SARS-CoV-2 patients, highlighting stereotyped naïve responses to this virus.
View Article and Find Full Text PDFB cells in human food allergy have been studied predominantly in the blood. Little is known about IgE B cells or plasma cells in tissues exposed to dietary antigens. We characterized IgE clones in blood, stomach, duodenum, and esophagus of 19 peanut-allergic patients, using high-throughput DNA sequencing.
View Article and Find Full Text PDFA goal of HIV vaccine development is to elicit antibodies with neutralizing breadth. Broadly neutralizing antibodies (bNAbs) to HIV often have unusual sequences with long heavy-chain complementarity-determining region loops, high somatic mutation rates and polyreactivity. A subset of HIV-infected individuals develops such antibodies, but it is unclear whether this reflects systematic differences in their antibody repertoires or is a consequence of rare stochastic events involving individual clones.
View Article and Find Full Text PDFEstrogen receptor (ER) β plays a critical role in endometriosis progression because cytoplasmic ERβ stimulates proinflammatory signaling in ectopic lesions and prevents apoptosis to promote their survival. However, the role of "nuclear ERβ" in endometriosis progression is not known. This critical knowledge gap obscures our understanding of the full molecular etiology of ERβ-mediated endometriosis progression.
View Article and Find Full Text PDFAntigenic exposures at epithelial sites in infancy and early childhood are thought to influence the maturation of humoral immunity and modulate the risk of developing immunoglobulin E (IgE)-mediated allergic disease. How different kinds of environmental exposures influence B cell isotype switching to IgE, IgG, or IgA, and the somatic mutation maturation of these antibody pools, is not fully understood. We sequenced antibody repertoires in longitudinal blood samples in a birth cohort from infancy through the first 3 years of life and found that, whereas IgG and IgA show linear increases in mutational maturation with age, IgM and IgD mutations are more closely tied to pathogen exposure.
View Article and Find Full Text PDFThe steroid receptor coactivator (SRC)-1 isoform/estrogen receptor (ER)-β axis has an essential role in endometriosis progression. In this context, therefore, bufalin was employed as a 'tool compound' to evaluate inhibitors of SRC in alternative endometriosis treatment. Bufalin effectively suppressed the growth of primary human endometrial stroma cells isolated from endometriosis patients compared to women without endometriosis and immortalized human endometrial epithelial and stromal cells expressing the SRC-1 isoform compared to their parental cells , compared to the vehicle, bufalin treatment significantly suppressed the growth of endometriotic lesions in mice with surgically induced endometriosis because bufalin disrupted the functional axis of SRC-1 isoform/ERβ by increasing SRC-1 isoform protein stability, hyperactivating the transcriptional activity of the SRC-1 isoform and degrading the ERβ protein by proteasome 26S subunit, non-ATPase 2 in endometriotic lesions.
View Article and Find Full Text PDFCommon variable immune deficiency (CVID) is the most common symptomatic primary immune deficiency, affecting ~1 in 25,000 persons. These patients suffer from impaired antibody responses, autoimmunity, and susceptibility to lymphoid cancers. To explore the cellular basis for these clinical phenotypes, we conducted high-throughput DNA sequencing of immunoglobulin heavy chain gene rearrangements from 93 CVID patients and 105 control subjects and sorted naïve and memory B cells from 13 of the CVID patients and 10 of the control subjects.
View Article and Find Full Text PDFBackground: B cells expressing IgE contribute to immunity against parasites and venoms and are the source of antigen specificity in allergic patients, yet the developmental pathways producing these B cells in human subjects remain a subject of debate. Much of our knowledge of IgE lineage development derives from model studies in mice rather than from human subjects.
Objective: We evaluate models for isotype switching to IgE in human subjects using immunoglobulin heavy chain (IGH) mutational lineage data.
J Allergy Clin Immunol
January 2016
Background: The frequencies, cellular phenotypes, epitope specificity, and clonal diversity of allergen-specific B cells in patients with food allergy are not fully understood but are of major pathogenic and therapeutic significance.
Objective: We sought to characterize peanut allergen-specific B-cell populations and the sequences and binding activities of their antibodies before and during immunotherapy.
Methods: B cells binding fluorescently labeled Ara h 1 or Ara h 2 were phenotyped and isolated by means of flow cytometric sorting from 18 patients at baseline and 13 patients during therapy.
Proc Natl Acad Sci U S A
January 2015
Adaptive immune responses in humans rely on somatic genetic rearrangements of Ig and T-cell receptor loci to generate diverse antigen receptors. It is unclear to what extent an individual's genetic background affects the characteristics of the antibody repertoire used in responding to vaccination or infection. We studied the B-cell repertoires and clonal expansions in response to attenuated varicella-zoster vaccination in four pairs of adult identical twins and found that the global antibody repertoires of twin pair members showed high similarity in antibody heavy chain V, D, and J gene segment use, and in the length and features of the complementarity-determining region 3, a major determinant of antigen binding.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2014
T-cell receptor (TCR) diversity, a prerequisite for immune system recognition of the universe of foreign antigens, is generated in the first two decades of life in the thymus and then persists to an unknown extent through life via homeostatic proliferation of naïve T cells. We have used next-generation sequencing and nonparametric statistical analysis to estimate a lower bound for the total number of different TCR beta (TCRB) sequences in human repertoires. We arrived at surprisingly high minimal estimates of 100 million unique TCRB sequences in naïve CD4 and CD8 T-cell repertoires of young adults.
View Article and Find Full Text PDF[Purpose] The purpose of this study was to determine the effects of aquatic exercise on pulmonary function of patients with spinal cord injury. [Subjects] The subjects were randomly allocated to an aqua group (n=10) and a land group (n=10). [Methods] Both groups trained for 60 minutes, 3 times a week for 8 weeks.
View Article and Find Full Text PDF[Purpose] This study evaluated the effects of water and land-based obstacle training on static balance of chronic stroke patients. [Subjects] The subjects were randomly allocated to an aqua group (n=15) and a land group (n=15). [Methods] Both groups trained for 40 minutes, 3 times a week for 12 weeks.
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