Mechanisms of Function of Tapasin, a Critical Major Histocompatibility Complex Class I Assembly Factor

For their efficient assembly in the endoplasmic reticulum (ER), major histocompatibility complex (MHC) class I molecules require the specific assembly factors transporter associated with antigen processing (TAP) and tapasin, as well as generic ER folding factors, including the oxidoreductases ERp57 and protein disulfide isomerase (PDI), and the chaperone calreticulin. TAP transports peptides from the cytosol into the ER. Tapasin promotes the assembly of MHC class I molecules with peptides. The formation of disulfide-linked conjugates of tapasin with ERp57 is suggested to be crucial for tapasin function. Important functional roles are also suggested for the tapasin transmembrane and cytoplasmic domains, sites of tapasin interaction with TAP. We show that interactions of tapasin with both TAP and ERp57 are correlated with strong MHC class I recruitment and assembly enhancement. The presence of the transmembrane/cytosolic regions of tapasin is critical for efficient tapasin–MHC class I binding in interferon-γ-treated cells, and contributes to an ERp57-independent mode of MHC class I assembly enhancement. A second ERp57-dependent mode of tapasin function correlates with enhanced MHC class I binding to tapasin and calreticulin. We also show that PDI binds to TAP in a tapasin-independent manner, but forms disulfide-linked conjugates with soluble tapasin. Thus, full-length tapasin is important for enhancing recruitment of MHC class I molecules and increasing specificity of tapasin–ERp57 conjugation. Furthermore, tapasin or the TAP/tapasin complex has an intrinsic ability to recruit MHC class I molecules and promote assembly, but also uses generic folding factors to enhance MHC class I recruitment and assembly.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79259/1/j.1600-0854.2009.01025.x.pd

Depression, anxiety and stress among COVID positive pregnant women

Background: Impact of the news that patient is covid positive may increase the risk of depression and anxiety among the vulnerable population such as pregnant women. Aims of the study were to estimate the prevalence of depression, anxiety and stress among covid positive pregnant women. To evaluate the demographic and obstetric factors contributing to the psychological manifestations in covid positive pregnant women.Methods: A cross sectional descriptive study was conducted at a tertiary hospital of North Kerala from July to August 2020. The demographic and factors were recorded and DASS 21 self-reported questionnaire was used to assess depression, anxiety and stress.Results: We found that using the DASS 21 scoring system, 37.5% out of the 120 study subjects were having psychological symptoms either of depression, anxiety or stress. Depression was seen in 32 (26.7%), anxiety in 29 (24.2%) and stress in 14 (11.7%) of the study participants. The psychological symptoms of depression and anxiety were more pronounced in those with low education, unemployed and in the first and third trimester of pregnancy.Conclusions: The current study shows that COVID-19 positive pregnant women have a high prevalence of depression and anxiety. Our findings can be used to formulate psychological interventions to improve mental health and psychological resilience during the COVID-19 pandemic

Effects of receptor dimerization on the interaction between the class I major histocompatibility complex-related Fc receptor and IgG

The neonatal Fc receptor (FcRn) transports maternal IgG from ingested milk in the gut to the bloodstream of newborn mammals. An FcRn dimer was observed in crystals of the receptor alone and of an FcRn-Fc complex, but its biological relevance was unknown. Here we use surface plasmon resonance-based biosensor assays to assess the role of FcRn dimerization in IgG binding. We find high-affinity IgG binding when FcRn is immobilized on a biosensor chip in an orientation facilitating dimerization but not when its orientation disrupts dimerization. This result supports a model in which IgG-induced dimerization of FcRn is relevant for signaling the cell to initiate endocytosis of the IgG-FcRn complex

Characterization of the Interaction between the Herpes Simplex Virus Type I Fc Receptor and Immunoglobulin G

Herpes simplex virus type I (HSV-1) virions and HSV-1-infected cells bind to human immunoglobulin G (hIgG) via its Fc region. A complex of two surface glycoproteins encoded by HSV-1, gE and gI, is responsible for Fc binding. We have co-expressed soluble truncated forms of gE and gI in Chinese hamster ovary cells. Soluble gE-gI complexes can be purified from transfected cell supernatants using a purification scheme that is based upon the Fc receptor function of gE-gI. Using gel filtration and analytical ultracentrifugation, we determined that soluble gE-gI is a heterodimer composed of one molecule of gE and one molecule of gI and that gE-gI heterodimers bind hIgG with a 1:1 stoichiometry. Biosensor-based studies of the binding of wild type or mutant IgG proteins to soluble gE-gI indicate that histidine 435 at the CH2-CH3 domain interface of IgG is a critical residue for IgG binding to gE-gI. We observe many similarities between the characteristics of IgG binding by gE-gI and by rheumatoid factors and bacterial Fc receptors such as Staphylococcus aureus protein A. These observations support a model for the origin of some rheumatoid factors, in which they represent anti-idiotypic antibodies directed against antibodies to bacterial and viral Fc receptors

Why do women in India not use public toilets?: patterns and determinants of usage by women in Warangal City

This paper is part of an extended study to assess the needs of women for public toilets (PT) and sanitation facilities in the city of Warangal, Telangana, India. A quantitative dip-stick study with a sample size of 197 women followed by 21 in-depth interviews was undertaken among a cross-section of women from various walks of life, different ages and qualifications. From the content analysis of the interviews and network analysis of the most commonly co-occurring words, the broad themes that emerged as sanitation needs of women in public spaces were related to high demand for exclusive toilets for women with specific facilities and caretakers who collect money and keep the toilets clean, with particular need for women caretakers to add to the feeling of security. A strong need greater number of well-maintained sanitation facilities in places such as bus stops and railway stations and access to the toilets from main roads rather from interior roads were other aspects that emerged

New Frontier in Hypericin-Mediated Diagnosis of Cancer with Current Optical Technologies

Photosensitizers (PSs) have shown great potentials as molecular contrast agents in photodynamic diagnosis (PDD) of cancer. While the diagnostic values of PSs have been proven previously, little efforts have been put into developing optical imaging and diagnostic algorithms. In this article, we review the recent development of optical probes that have been used in conjunction with a potent PS, hypericin (HY). Various fluorescence techniques such as laser confocal microscopy, fluorescence urine cytology, endoscopy and endomicroscopy are covered. We will also discuss about image processing and classification approaches employed for accurate PDD. We anticipate that continual efforts in these developments could lead to an objective PDD and complete surgical clearance of tumors. Recent advancements in nanotechnology have also opened new horizons for PSs. The use of biocompatible gold nanoparticles as carrier for enhanced targeted delivery of HY has been attained. In addition, plasmonic properties of nanoparticles were harnessed to induce localized hyperthermia and to manage the release of PS molecules, enabling a better therapeutic outcome of a combined photodynamic and photothermal therapy. Finally, we discuss how nanoparticles can be used as contrast agents for other optical techniques such as optical coherence tomography and surface-enhanced Raman scattering imaging

Identification of domain boundaries within the N‐termini of TAP1 and TAP2 and their importance in tapasin binding and tapasin‐mediated increase in peptide loading of MHC class I

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141680/1/imcb200564.pd