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At least 19 recordsLinked to original sources

Actin filaments in sensory hairs of inner ear receptor cells.

Receptor cells in the ear are excited through the bending of sensory hairs which project in a bundle from their surface. The individual stereocilia of a bundle contain filaments about 5 nm in diameter. The identity of these filaments has been investigated in the crista ampullaris of the frog and guinea pig by a technique of decoration with subfragment-1 of myosin (S-1). After demembranation with Triton X-100 and incubation with S-1, "arrowhead" formation was observed along the filaments of the stereocilia and their rootlets and also along filaments in the cuticular plate inside the receptor cell. The distance between attached S-1 was 35 nm and arrowheads pointed in towards the cell soma. It is concluded that the filaments of stereocilia are composed of actin.

Actin Cytoskeleton

Immunological studies of T-cell receptors. II. Limited polymorphism of idiotypic determinants on T-cell receptors specific for major histocompatibility complex alloantigens.

These studies explore the extent of genetic polymorphism in the expression of anti-MHC receptors by T cells in different strains of rats. This question was approached with the use of the model of specifically induced GVH resistance in F1 rats which has been shown to reflect a specific T-cell mediated immune response against parental strain T cell anti-MHC receptors specific for host alloantigens. When A/B F1 rats derived from MHC incompatibile matings are immunized with lymphocytes from one parental strain (A they display a specific resistance to anti-B GVH reactivity caused by T cells from that parental strain, but not anti-AGVH reactions from the other. In addition, they resist anti-B GHV reactivity by T cells from third-party donors (C, D, E,...), a finding taken to indicate that the idiotypes of anti-MHC receptors on T cells, recognized by other T cells, show little or no polymorphism. This conclusion suggests that anti-MHC receptors are shared in the species and may be encoded, at least partially, by germ-line genes.

Animals

Proximity between LAG-3 and the T cell receptor guides suppression of T cell activation and autoimmunity.

Therapeutically targeting pathogenic T cells in autoimmune diseases has been challenging. Although LAG-3, an inhibitory checkpoint receptor specifically expressed on activated T cells, is known to bind to major histocompatibility complex class II (MHC class II), we demonstrate that MHC class II interaction alone is insufficient for optimal LAG-3 function. Instead, LAG-3's spatial proximity to T cell receptor (TCR) but not CD4 co-receptor, facilitated by cognate peptide-MHC class II, is crucial in mediating CD4+ T cell suppression. Mechanistically, LAG-3 forms condensate with TCR signaling component CD3ε through its intracellular FSAL motif, disrupting CD3ε/lymphocyte-specific protein kinase (Lck) association. To exploit LAG-3's proximity to TCR and maximize LAG-3-dependent T cell suppression, we develop an Fc-attenuated LAG-3/TCR inhibitory bispecific antibody to bypass the requirement of cognate peptide-MHC class II. This approach allows for potent suppression of both CD4+ and CD8+ T cells and effectively alleviates autoimmune symptoms in mouse models. Our findings reveal an intricate and conditional checkpoint modulatory mechanism and highlight targeting of LAG-3/TCR cis-proximity for T cell-driven autoimmune diseases lacking effective and well-tolerated immunotherapies.

Animals

[Immunoglobulins and sheep red cell receptors in human lymphoblastoid cell lines simultaneously carrying Epstein-Barr virus and cytomegalovirus genomes].

In this communication we attempt to characterize the principal immunological properties of 3 human lymphoblastoid cell lines (LCL) established in our laboratory which carry both the EBV and CMV genomes. The data obtained suggests that two LCL are representative of B lymphocytes while the other LCL has a mixed cell population with the majority being of the B type. The reasons for this heterogeneity are discussed. It is suggested that CMV may also transform thymus-independent (B) lymphocytes.

Binding Sites, Antibody

Evaluation of the possible role of B cell receptors in the tendency of B cells to migrate into follicles in mice and chickens.

Chicken spleen and bursa cells were examined for the percentage of Fc receptor-bearing cells. Rosette formation was done with chicken 7S antibody-sensitized sheep erythrocytes and was inhibited by heat-aggregated chicken Ig. In the spleen, the percentage was found to increase with age to approximately 26% at 7 to 12 weeks. In contrast, only 3 to 5% of bursa cellss at this age demonstrated Fc receptors. Sleens from bursectomized chickens had 7--10% Fc receptor-bearing cells. In an attempt to determine a possible role of the C3 receptor on migration patterns, the effect of cobra venom factor (CVF) on the localization of transferred lymphoid cells was examined. Pretreatment of recipients with enough CVF to lower mean C3 levels to 11% of controls failed to affect follicular B cell localization in mice at either 24 or 48 h after transfer. Localization of thymus or bursa cells in chickens was similarly unaffected by CVF pretreatment. The possible roles of Fc and C3 receptors on migration of B lymphocytes into follicles and germinal centers were discussed.

Animals

Neighborhood enrichment for the identification of antigen-specific T-cell receptors.

Understanding T-cell receptor (TCR) specificity is not only essential for fundamental research, but could open up novel avenues for diagnostics, cancer immunotherapy, and the targeted treatment of autoimmune diseases. The immune system responds to challenges through groups of T-cells with similar TCR sequences. In recent years, searching for TCRs with an enrichment of similar sequences - neighbors - in a TCR repertoire has become a standard procedure for antigen-specific TCR identification. This study provides a systematic comparison of computational algorithms-ALICE, TCRNET, GLIPH2, and tcrdist3-that leverage neighborhood enrichment for antigen-specific TCR identification. Using published murine datasets from Lymphocytic choriomeningitis virus (LCMV) infection and novel datasets from Sputnik V vaccination and Mycobacterium tuberculosis (Mtb) infection, we evaluated the performance of these algorithms. To facilitate reproducible analysis, we developed TCRgrapher, an R library that integrates these pipelines into a user-friendly framework. TCRgrapher enables efficient identification of antigen-specific TCRs from single repertoire snapshots and supports flexible parameter customization. Our comparative analysis revealed that ALICE and TCRNET consistently outperformed GLIPH2 and tcrdist3 across most datasets, achieving higher area under precision-recall curve. While murine datasets provide valuable insights into algorithm performance, caution is advised when extrapolating these results to other species or different experimental conditions. TCRgrapher is freely available on GitHub (https://github.com/KseniaMIPT/tcrgrapher), offering researchers a robust tool for investigating TCR specificity and advancing immunological studies.

Animals

[Fc-gamma-receptor cells and rheumatoid arthritis].

Certain blood lymphocytes of patients suffering from rhumatoid arthritis (RA) and or control subjects, can be detected using a rosette technique in the presence of erythrocyte antibody compounds (EA). The EA rosettes demonstrate the presence of cells having a receptor for the Fc fragment of the IgG's (Fc-receptor). A significant increase in highly active EA rosettes during RA was demonstrated using six EA compounds differing according to the type of erythrocyte and the quantity of sensitizing antibody. These highly active EA rosettes correspond to the case in which few antiserum molecules cover the erythrocytes. Their high level in RA may correspond to an increased number of Fc-receptor cells or to a stronger linkage of EA compounds. The cells forming EA rosettes are responsible for the resulting cell antibody cytotoxicity that seems to change little during rhumatoid disease. However, the very special behavior of Fc-receptor lymphocytes incubated in vitro suggests that the IgG receptors are modulated by the immune compounds present during RA.

Adult

Observations on the cytolemma of the olfactory receptor cell in the newt. 1. Freeze replica analysis.

The fine structure of the cytolemma of olfactory receptor cells in the newt was studied by the freeze-fracture replica method. Two kinds of receptor cells were recognized, namely ciliated cells (ciliary type) and non-ciliated cells (microvilli type). The cytolemma of olfactory knobs as well as their processes from both types of receptor cells showed an abundance of large membrane particles 80 approximately 110 A in diameter. The large square aggregation of membrane particles, 0.1 x 0.1 micron to 0.2 x 0.3 micron in size, consisting of 50 approximately 100 cuboidal subunits, were found in the cytolemma of the dendrite. A structural model of aggregation is presented. The soma of the receptor cell revealed large pitted membrane particles about 140 A in diameter. These particles are possibly the morphologic counterpart to ionophores which have been proposed by electrophysiological studies.

Animals

Response of Aplysia statocyst receptor cells to physiologic stimulation.

1. The electrical responses of Aplysia statocyst receptor cells were investigated using intracellular micro-electrodes. These ciliated mechanoreceptor cells were stimulated by downward tilting about a horizontal axis. 2. Tilting so that the receptor cell was excited produced a depolarizing receptor potential which, if large enough, could generate action potentials. 3. Large fluctuations in membrane potential were evident during depolarizing receptor potentials and were reduced or sometimes absent when a cell was tilted upward. Power-density spectra of the noise voltage revealed that most of the energy added by downward tilt is contained in frequency components below 3 Hz. 4. Removing synaptic input to the receptor cells by cutting the statocyst nerve or adding excess Mg2+ to the bath did not abolish the increase in fluctuations caused by downward, excitatory tilts. 5. The depolarizing receptor potential was often associated with a decrease in membrane resistance as measured with constant current pulses using a bridge circuit. 6. Replacing most of the Na+ in the bath with either Tris or Mg2+ abolished both potential and resistance changes caused by downward tilt. These results indicate that an increased permeability to Na+ underlies the receptor potential.

Animals

Unitary recordings of near threshold responses of receptor cells in the olfactory mucosa of the frog.

1. Receptor cell activity in the frog's eminentia olfactoria was recorded using metal-filled micro-electrodes. 2. Several units discharged spontaneously with a mean frequency lower than 0.2 spikes per sec, or were silent in periods of up to 5 min. The other units displayed spontaneous activities between 0.2 and 1.05 spikes per sec; their activity could be modelled with a Poisson process. 3. Near-threshold responses to odour stimulation were investigated, considering several stimulations within a small concentration range. Low concentration stimulations were sometimes followed by a response, sometimes not. The concept of response probability is introduced to describe this incertitude. 4. The distribution of the number of spikes in several odour trials at low concentrations showed a reasonable agreement with two types of Poisson distribution. 5. The findings are discussed in connexion with receptor cell sensitivity and the excitation of second order neurones in the bulb.

Action Potentials

Differentiation of olfactory receptor cells in organ culture.

Presumptive olfactory mucosa was excised from the heads of rat fetuses in the eleventh and twelfth days of gestation and explanted in organ cultures. At the time of explanation, the presumptive olfactory cells were recognizable by their long narrow apical processes and basally located nuclei. However at this stage they were in an early phase of differentiation as indicated by the large numbers of free ribosomes and virtual absence of microtubules and cilia in the apical cytoplasm. After three to eight days in culture, there was a progressive increase in the total number of cells in the epithelium. Differentiation in olfactory receptor cells was detectable by the appearance in the apical processes of axially oriented microtubules and centrioles or basal bodies, some of which generated cilia. At their basal ends, the cytoplasm narrowed into axons and bundles of these axons, arranged in the unique manner of olfactory nerve axons, entered the connective tissue. Olfactory receptor cells, as defined by morphological criteria, differentiated under suitable organ culture conditions in the absence of any tissue from the central nervous system.

Animals

Binding of purified, soluble major histocompatibility complex polypeptide chains onto isolated T-cell receptors. I. Reactivity against allo- and self-determinants.

In this study, we tried to get information about the fine antigen-binding ability of purified, soluble, idiotype-positive T-cell receptor molecules. Lewis anti-DA T-cell receptors were purified from normal Lewis serum by the use of anti-idiotypic immunosorbent and sodium dodecyl sulfate-polyacrylamide gel, and were coupled to cyanogen bromide-activated Sepharose 4B. In parallel, Lewis anti-DA, Lewis anti-BN, and DA anti-Lewis alloantibody immunosorbents were prepared. The major Ag-B chain (44,000 daltons) and the two polypeptide chains (34,000 and 27,000 daltons) of Ia were purified from Lewis, DA, and BN lymphocytes and absorbent on the above-mentioned immunosorbents. We found that the major Ag-B chain as well as the two Ia chains were bound to the alloantibody columns if they were derived from the corresponding allogeneic strain. No retaining ability for self-major histocompatibility complex (MHC) or third-party MHC chains was noted with the alloantibody immunosorbents. When using immunosorbents made up of idiotypic T-cell receptors, only two MHC polypeptides of the relevant allo-MHC type were retained, namely, the Ag-B and the heavy Ia chains. No detectable activity was observed when testing the same column for reactivity against third-party MHC polypeptide chains. However, the Lewis anti-DA T-cell receptors could be shown to display weak, but significant, reactivity toward one Lewis MHC polypeptide chain, that is, the heavy chain of Ia type.

Animals

The effect of cell synchronization upon the detection of T and B lymphoid cell receptors on two continuous lymphoid cell lines.

In the present study, the effect of the cell synchronization on the detection of T and B cell surface markers of two continuous lines of lymphoid cells (FL-74 and CT45-S) was examined. Suspension cultures were synchronized by deprivation of isoleucine and surface markers were quantitated by T rosette formation with guinea pig erythrocytes (E) and B rosette formation with an erythrocyte-antibody-complement (EAC) complex. After 24 hr, cells were resuspended in complete culture medium. Virtually 100% of FL-74 cells expressed the T cell marker at time 0, with a progressive decline to 80% at saturation density. A bell-shaped curve for expression of the EAC marker on CT45-S cells was seen with maximum expression in the logarithmic phase of the growth cycle. Spent culture medium was examined for the presence of free soluble receptor. Preincubation of E and EAC in appropriate old medium resulted in 42% inhibition of E rosettes and 42% inhibition of EAC rosettes with FL-74 and CT45-S cells, respectively. Thus quantitation of lymphocyte subpopulations as B, T or null cells with these cellular markers may be influenced by the age of the cell examined, phase of the cell cycle and the amount of free receptor present in the surrounding medium.

B-Lymphocytes

Biochemical study of KB-cell receptor for adenovirus.

Three different approaches were used in an attempt to characterize the KB-cell receptor for adenovirus: affinity chromatography, immunoadsorption and cross-linking with a cleavable bifunctional reagent. The first system used an affinity gel consisting of adenovirus-fibre projection linked to Sepharose matrix by an intermediate bis(aminopropyl)amine arm, the amino groups of the fibre ligand being preserved by prior citraconylation. The second system consisted of adenovirus complete penton capsomere attached to anti-(penton base) antibody and cross-linked to polyacrylamide particles with glutaraldehyde. In this latter affinity model, the penton-fibre projection was appropriately oriented outwards, as in the virus particle. Both affinity systems permitted isolation from a KB-cell plasma-membrane extract of fibre-binding and penton-fibre-binding protein material, which inhibited adenovirus attachment. The penton-immunoadsorbent appeared more efficient and more specific than the affinity column of fibre-bis(aminopropyl)amino-Sepharose gel in specific activity of inhibition of adenovirus attachment. The third method consisted of reversibly cross-linking KB-cell receptor proteins with adenovirus particles by means of a cleavable di-imidoester and isolation of the complexes by sucrose-density-gradient centrifugation. Polypeptide analysis on sodium dodecyl sulphate/polyacrylamide gel of labelled KB-cell surface proteins, selected by the different procedures, showed that three major protein subunits of 78000, 42000 and 34000mol.wt. were common to the three selection systems. A possible model for the structure and function of the KB-cell receptor for adenovirus is discussed.

Adenoviruses, Human