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At least 145 records · Page 8Linked to original sources

PubMed1984

Antigen-specific HLA-restricted human T-cell lines. I. An MT3-like restriction determinant distinct from HLA-DR.

The results presented provide evidence that the HLA specificity known as MT3, BR4, or Hon7 can serve as a restriction epitope for the proliferation of certain T cells responding to mumps viral antigen. This restriction determinant was found to be HLA-linked in family studies, and to segregate centromeric to a crossover between HLA-B and DR in one family. In the population studied, the specificity was found to be associated with the DR antigens DR4, DR7, and DRw9, which are known to be associated with MT3. The ability of accessory cells to present mumps antigen in the context of this supertypic restriction determinant was blocked by a monoclonal antibody specific for MT3. Since MT3 (BR4, Hon7) has been shown to be expressed on molecules distinct from DR, our experiments suggest that such molecules are functionally important in antigen presentation to T cells.

Antibodies, Monoclonal↗

PubMed1983

H-2-restricted graft-versus-host reaction: foreign determinants and restriction elements.

Nylon-wool-purified T cells from radiation chimeras cause a lethal graft-versus-host reaction (GVHR) in irradiated, bone-marrow-protected recipients only if the recipient shares a restriction element with the T-cell donor and also expresses antigens foreign to the donor. Class I molecules (H-2K and H-2D) can act as restriction elements, but restriction to class II molecules could not be demonstrated. However, class II molecules as well as H-2K and some non-H-2 determinants could serve as foreign antigens.

Animals↗

PubMedDate not supplied

Food restriction in female Wistar rats. VI. Effect of reduced glutathione on the proliferative response of splenic lymphocytes from ad libitum fed and food restricted animals.

The effect of reduced glutathione (GSH) on the proliferative response of splenic lymphocytes from young, adult and old ad libitum (AL) fed as well as from old food-restricted rats was investigated. Food restriction was applied on an every-other-day schedule (EOD) starting from the age of 3.5 months. As was expected, the cells from EOD fed animals responded to concanavalin A (Con A) much better than those from age-matched ad libitum fed rats. The presence of the antioxidant GSH in the culture medium increased the response of lymphocytes in all the models taken into account; furthermore, it decreased the differences due to aging and application of food restriction. According to present knowledge, mitogenic stimulation induces free radical production, and GSH has, among others, a strong antioxidant activity. Thus, present data suggest that splenocytes from EOD animals tolerated the peroxidative stress resulting from mitogenic stimulation better than those from AL fed ones.

Journal Article↗

PubMed2006

Sulphonic acid strong cation-exchange restricted access columns in sample cleanup for profiling of endogenous peptides in multidimensional liquid chromatography. Structure and function of strong cation-exchange restricted access materials.

In this work, the pore structural parameters and size exclusion properties of LiChrospher strong cation-exchange and reverse phase restricted access materials (RAM) are analysed. The molecular weight size exclusion limit for polystyrenes was found to be about 17.7 kDa, while for standard proteins, the molecular weight size exclusion limit was higher, at approximately 25 kDa. The average pore diameter on a volume basis calculated from the pore network model changes from 8.5 nm (native LiChrospher) to 8.6 nm (diol derivative) to 8.2 nm (sulphonic acid derivative) to 6.9 nm (n-octadecyl derivative). Additional characterisations were performed on restricted access materials with nitrogen sorption at 77 K, water adsorption at 25 degrees C, intrusion-extrusion of water (in order to evaluate the hydrophobic properties of the pores of the hydrophobic RAM), and zeta potential measurements by microelectrophoresis. For peptide analysis out of the biofluids, the strong cation-exchange functionality seems to be particularly suitable mainly because of the high loadability of the strong cation-exchange restricted access material (SCX-RAM) and the fact that one can work under non-denaturing conditions to perform effective chromatographic separations. For bacitracin, the dynamic capacity of the SCX-RAM columns does not reach its maximum value in the analysed range. For lysozyme, the dynamic capacity reaches a value of 0.08 mg/ml of column volume before column is overloaded. Additionally, the proper column operating conditions that lead to the total effective working time of the RAM column to be equal to approximately 500 injections (depending on the type of sample), is comprehensively described. The SCX-RAM column was used in the same system analysing urine samples for the period of 1 month (approximately 150 injections) with run-to-run reproducibility below 5% RSD and below 10% RSD for the relative fractions.

Cation Exchange Resins↗

PubMed2002

Culture filtrate specific H-2(b) restricted CD8+ T cells activated in vivo by Mycobacterium tuberculosis or bovis BCG recognize a restricted number of immunodominant peptides.

We previously demonstrated that Bacillus Calmette-Guerin (BCG) immunization activated D(b) restricted CD8+ cytolytic T lymphocyte (CTL) recognizing target cells incubated with mycobacterial culture filtrate. Here, we show that in vitro restimulation of spleen cells from BCG vaccinated or Mycobacterium tuberculosis infected mice with culture filtrate antigens leads to the appearance of a high percentage of D(b) restricted IFNgamma synthesizing CD8+ T cell blasts. Transporter associated protein-2 mutated RMA-S cells incubated with soluble culture filtrate proteins had their MHC class I D(b) but not K(b) molecules stabilized at the surface indicating that only D(b) ligands might be generated by antigen presenting cells. MHC class I bound peptides were acid eluted from the surface of RMA-S cells incubated with M. tuberculosis culture filtrate proteins. The crude peptide preparation was able to sensitize RMA-S cells for recognition by culture filtrate-specific cytolytic T cells. Peptides were subsequently fractionnated by reverse-phase high performance liquid chromatography and the main biological activity was identified in two fractions. These results provide a further evidence that the processing of exogenous culture filtrate proteins in vitro leads to the presentation of a restricted number or even a single immunodominant peptide to culture filtrate-specific CD8+ T cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Isolation and partial purification of a novel type II restriction endonuclease Bsu121 I, from Bacillus subtilis. Bsu121I, a type II restriction endonuclease from Bacillus subtilis.

A new type II restriction endonuclease which we designated as Bsu121I has been isolated from gram-positive bacterium Bacillus subtilis strain 121 and partially purified. The restriction endonuclease was isolated from cell extracts using step-wise purification through ammonium sulfate precipitation, followed by phosphocellulose column chromatography. SDS-PAGE profile showed denatured molecular weights (23 and 67 kDa) of the endonuclease. The partially purified enzyme restricted pBR322 DNA into two fragments of 3200 and 1700 bp. The endonuclease activity required Mg(+2) as cofactor like other type II endonucleases.

Bacillus subtilis↗

PubMed2001

Cancer genesis: stem tumour cells as an MHC-null/HSP70 - very high 'primordial self' escaping both MHC-restricted and MHC-non- restricted immunesurveillance.

I have previously assumed that in tumours there are stem cells, that owing to the morphophysiologic properties shared with embryonal cells I have defined as 'para-embryonal' cells (PECs). Owing to a blocking mutation, PECs might be able to express only the genic program upstream from the block, but not that downstream. As a consequence, PECs might lack in genic differentiated products, such as MHC molecules, and might be very rich in primitive genic products, such as HSP70 molecules. Like embryonal cells, PECs might carry out induction on adjoining hyperplastic cells, thus transforming them, only phenotypically, into 'differentiated para-embryonal cells' (DPECs), endowed with both MHC and HSP70 molecules. In such a way, nuclei of MHC-non-expressing/HSP70-high expressing stem tumour cells might be surrounded by layers of MHC-expressing/HSP70-expressing non-stem tumour cells. Such a structural tumour organization, actually found by C. Cordon Cardo et al. with regard to the MHC molecule expression, might be responsible for interference phenomena versus the MHC-non-restricted immune cells, such as macrophages and NK cells. So, these cells, the only potentially able to recognize and eliminate MHC-non-expressing stem tumour cells (PECs), might spare them, thus rendering cancer a biological process without any natural immunological solution. Now, I would like to theorically demonstrate that cancer might be a process without immunological solution from the very beginning: the first stem tumour cell might be tolerated as a sort of 'primordial self' because of its MHC-null/HSP70-very high phenotype, recognizable by neither the MHC-restricted nor the MHC-non-restricted immunesurveillance systems of the host. Possible biological roles of HSP70 molecules might account for the immunesurveillance escape of stem tumour cells. Existence of these cells appears to be confirmed by the recent experiments of immunotherapy with autologous tumour-specific HSPs carried out by P. K. Srivastava; moreover, their 'self' nature appears to be confirmed by the most recent experiments of compatible bone marrow allograft carried out by A. M. Carella. On this ground, the main steps for a resolutive antitumour immunotherapy are proposed.

HSP70 Heat-Shock Proteins↗

PubMed1978

Complement C3 convertase: cell surface restriction of beta1H control and generation of restriction on neuraminidase-treated cells.

The alternative or properdin pathway of complement is primarily controlled by the endopeptidase C3b inactivator (C3bINA) and the nonproteolytic glycoprotein beta1H. The molecular mechanisms of control were investigated by performing binding studies of radiolabeled complement proteins to C3b bearing sheep erythrocytes (E(S)C3b). C3b was found to have distinct binding sites for beta1H, C3bINA, Factor B, and properdin. beta1H binding increased C3bINA binding 30-fold, while Factor B binding prevented C3bINA action on C3b and was competitive with beta1H binding. Properdin binding, which facilitates Factor B interaction with C3b, had no effect on the beta1H and C3bINA sites. Activators such as rabbit erythrocytes (E(R)) have previously been shown to interfere with the effectiveness of the control by C3bINA and beta1H, thereby allowing unrestricted formation of C3 convertase. Such restriction of control does not occur on the surface of E(S), a nonactivator of the alternative pathway. On the basis of comparative binding studies, restriction of control is explained entirely by reduced binding of beta1H to E(R)C3b relative to E(S)C3b. Access of properdin, Factor B, C3bINA, and the Fab fragment of anti-C3 to the two cell types was unrestricted. Restriction of beta1H control could be generated on the surface of E(S) by removal of cell-surface sialic acid with neuraminidase (acylneuraminyl hydrolase; EC 3.2.1.18). This enzymatic treatment converted E(S) from a nonactivator to an activator of the alternative pathway.

Binding Sites↗

PubMed1983

Igh variable region-restricted T cell interactions. Genetic restriction of an antigen-specific suppressor inducer factor is imparted by an I-J+ antigen-nonspecific molecule.

Immunized Ly-1 T cells secrete an antigen-specific molecule that will induce Ly-2+ T cells to express suppressive activity. In two separate systems, factors that suppress the primary anti-sheep erythrocyte (SE) plaque-forming cell response of spleen cells in vitro (Ly-1 TsiF) or the contact sensitivity of azobenzenearsonate (ABA)-TsF1 consist of two macromolecules, one which binds antigen and is IJ-, the other which is I-J+ and does not bind antigen. Both of these chains are required for the factor's biological activity. These factors show a genetic restriction in their ability to induce suppression that is linked to the variable region of the Ig heavy chain gene complex (Igh-V). The I-J+ chain from the ABA-specific TsF1 could replace the I-J+ chain needed by the SE-specific Ly-1 TsiF for biological activity. Mixtures of ABA-binding chain with I-J+ material obtained from the SE-specific Ly-1 TsiF had no effect on the primary anti-SE response in vitro. In mixtures of SE antigen-binding chain from Ly-1 TsiF and I-J+ material from the ABA-specific TsF1, it is the I-J+ molecule that determined the factor's Igh-V restriction. Thus, the antigen-combining site of the factor determined the antigen specificity of this factor but is irrelevant to its Igh-V-linked genetic restrictions. The implications of these results for the idiotype network hypothesis are discussed.

Animals↗

PubMed1984

Thymus dictates major histocompatibility complex (MHC) specificity and immune response gene phenotype of class II MHC-restricted T cells but not of class I MHC-restricted T cells.

Athymic H-2b nude mice received grafts from C57BL/6 (Sendai virus and H-Y antigen cytotoxic T lymphocyte [CTL] responder type), bm1 (H-2Kb mutant, Sendai CTL nonresponder type), or bm12 (H-21-A mutant, H-Y CTL nonresponder type) neonates. In observations of the CTL response to H-Y, both recipients and thymus donors were female. All types of thymus engraftment resulted in mature H-2b splenic T lymphocyte surface phenotype in nude hosts. T cell immunocompetence (as measured by major histocompatibility complex [MHC] CTL responses to allogeneic cells) was restored, and induced nonresponsiveness to the MHC determinants of the engrafted thymus in the nude host. The CTL reaction to Sendai virus in both responder type C57BL/6 and nonresponder type bm1 neonatal thymuses allowed maturation of Sendai-specific, H-2Kb-restricted CTL. For the CTL reaction to H-Y, only responder type C57BL/6 thymuses restored the CTL response, whereas this was not achieved with thymuses from nonresponder type bm12 neonatal females. Results of double thymus (B6 and bm12) engraftment excluded the possibility that this latter effect was caused by suppression. In addition, athymic bm1 mice were engrafted with thymuses from either B6 (Sendai CTL responder type) or syngeneic bm1 neonates (Sendai CTL nonresponder type). Again, both types of neonate thymuses restored T cell competence as measured by MHC/CTL responses to allogeneic cells. However, neither responder B6 nor nonresponder bm1 neonate thymus grafts allowed maturation of Sendai-specific CTL. In conclusion, the thymus dictates MHC specificity and immune response gene phenotype of T cells restricted to class II MHC molecules but not of T cells restricted to class I MHC molecules.

Animals↗

PubMed1990

Human protectin (CD59), an 18-20-kD homologous complement restriction factor, does not restrict perforin-mediated lysis.

Human protectin (CD59) is an 18-20-kD membrane glycoprotein that restricts lysis of human erythrocytes and leukocytes by homologous complement. By directly incorporating protectin into membranes of heterologous cells we observed that protectin did not prevent perforin-mediated killing, whereas complement killing was effectively restricted. Further, no significant enhancement of cell-mediated killing or target killing by purified perforin was observed with anti-protectin antibodies. Thus, in contrast with complement lysis, restriction of lysis by protectin does not apply to cell-mediated killing.

Animals↗

PubMed2006

Identification of a novel HIV type 1 CRF01_AE cytotoxic T lymphocyte (CTL) epitope restricted by an HLA-Cw0602 allele and a novel HLA-A0206/peptide restriction.

This report describes specific T cell responses to HIV-1 CRF01_AE Env and A Gag peptides in 20 HIV-1 CRF01_AE-infected Thai individuals using an interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISpot) assay. Twenty-six potentially novel HLA class I-restricted CD8+ T cell epitopes were identified in 14/20 subjects. Fine mapping analysis using the chromium release cytotoxic T lymphocyte (CTL) assay revealed a novel HLA-Cw0602 restricted epitope of HIV-1 CRF01_AE Env (NAKTIIVHL) and a previously identified HIV-1 A Gag epitope (ATLEEMMTA) with a novel HLA-A0206 restriction.

CD8-Positive T-Lymphocytes↗

PubMed2002

Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period.

Four female and four male crew members, including two of the present authors (R. Walford and T. MacCallum)--seven of the crew being ages 27 to 42 years, and one aged 67 years--were sealed inside Biosphere 2 for two years. During seven eighths of that period they consumed a low-calorie (1750-2100 kcal/d) nutrient-dense diet of vegetables, fruits, nuts, grains, and legumes, with small amounts of dairy, eggs, and meat (approximately 12% calories from protein, approximately 11% from fat, and approximately 77% from complex carbohydrates). They experienced a marked and sustained weight loss of 17 +/- 5%, mostly in the first 8 months. Blood was drawn before entry into Biosphere 2, at many time-points inside it, and four times during the 30 months following exit from it and return to an ad libitum diet. Longitudinal studies of 50 variables on each crew member compared outside and inside values by means of a Bayesian statistical analysis. The data show that physiologic (e.g., body mass index, with a decrease of 19% for men and 13% for women; blood pressure, with a systolic decrease of 25% and a diastolic decrease of 22%), hematologic (e.g., white blood cell count, decreased 31%), hormonal (e.g., insulin, decreased 42%; T3, decreased 19%), biochemical (e.g., blood sugar, decreased 21%; cholesterol, decreased 30%), and a number of additional changes, including values for rT3, cortisol, glycated hemoglobin, plus others, resembled those of rodents or monkeys maintained on a calorie-restricted regime. Significant variations in several substances not hitherto studied in calorie-restricted animals are also reported (e.g., androstenedione, thyroid binding globulin, renin, and transferrin). We conclude that healthy nonobese humans on a low-calorie, nutrient-dense diet show physiologic, hematologic, hormonal, and biochemical changes resembling those of rodents and monkeys on such diets. With regard to the health of humans on such a diet, we observed that despite the selective restriction in calories and marked weight loss, all crew members remained in excellent health and sustained a high level of physical and mental activity throughout the entire 2 years.

Adaptation, Physiological↗

PubMed1982

HLA-D/DR restriction of Langerhans cell-dependent antigen activation of T lymphocytes. The same D/DR determinants are restriction elements on monocytes and Langerhans cells.

In previous studies we have shown that the response of T cells to antigen presented by epidermal Langerhans cells (LC) is restricted by products of the HLA-D region. An optimal antigen-specific response required that the LC used for antigen presentation shared both, or at least one, of the D/DR determinants of the T-cell donor. These studies were, however, disturbed by a strong allogeneic response induced by the foreign D/DR determinants of the LC. We report here that by separating the antigen-specific T cells from those that are alloreactive, a clearer picture of the D/DR restriction phenomenon may be obtained. Furthermore, the present studies demonstrate that the same D/DR determinants function as restriction elements on peripheral blood monocytes and LC.

Antigens↗

PubMed1984

Analysis of the (H-2b X H-2k)F1-restricted response to insulin. Ab alpha Ak beta hybrid Ia molecules restrict the response towards the glutamic acid A4 epitope.

The aim of these studies was to characterize the (H-2b X H-2k)F1-unique restriction element(s) responsible for presentation of bovine insulin (BI) to a long-term cultured T-cell line (BK-BI-1.2). (B10.BR X bm12)F1 spleen cells, which express a normal Ab alpha Ak beta molecule but a mutated Ak alpha Abm12 beta product on their cell surface, were perfectly able to act as BI-presenting cells. Antibody inhibition experiments with antibodies directed at I-Ak products revealed that monoclonal antibody 10-2.16, which reacts with the Ak beta polypeptide chain, abrogated BI-directed T-cell proliferation, whereas antibody H116-32.R5 with specificity for the Ak alpha chain was not inhibitory. These results identified the Ab alpha Ak beta complex as restriction structure. Recognition of BI in the context of the Ab alpha Ak beta molecule depended on the glutamic acid residue in position 4 of the A chain of bovine insulin. Twenty to twenty-five percent of the secondary proliferative response of (B10 X B10.BR)F1 lymph node T cells primed with BI in vivo was directed at the A4 determinant, suggesting that BK-BI-1.2 T blasts are representative of T-cell clones with measurable frequency. In (B10.BR X bm12)F1 mice, which lack a functional Ab alpha Ab beta restriction element, up to 80% of the proliferative response was dependent on the A4 epitope.

Animals↗

PubMed1982

HLA-D/DR restriction of proliferative T cell responses to antigen. Enrichment of antigen-specific T cell blasts and evidence of preferential HLA-D/DR restriction.

Antigen-specific T cell blasts may be separated from alloreactive cells on Percoll gradients. The absence of alloreactivity allowed us to study HLA-D/DR restriction of proliferative T cell responses towards PPD and HSV antigens using allogeneic antigen-presenting cells. An overriding impact of self HLA-D/DR determinants as restriction elements for in vivo sensitized T cells was demonstrated. Furthermore, evidence was obtained that the proliferative PPD response might be preferentially restricted by HLA-D/DR 1.

Antigens↗

PubMed1972

R factor-controlled restriction and modification of deoxyribonucleic acid: restriction mutants.

Restriction mutants of two different R factor-controlled host specificities (RI and RII) were isolated. All of the restriction mutants examined had a normal modification phenotype. No complementation was observed between the RI and RII host specificities. It is concluded that for each host specificity no protein subunit is shared by the restriction endonuclease and modification methylase.

Anti-Bacterial Agents↗

PubMed1968

Host-controlled restriction of T-even bacteriophages: relation of four bacterial deoxyribonucleases to restriction.

Escherichia coli strains B and K-12, which restrict growth of nonglucosylated T- even phage (T(*) phage), and nonrestricting strains (Shigella sonnei and mutants of E. coli B) were tested for levels of endonuclease I and exonucleases I, II, and III, by means of in vitro assyas. Cell-free extracts freed from deoxyribonucleic acid (DNA) were examined with three substrates: E. coli DNA, T(*)2 DNA, and T2 DNA. Both restricting and nonrestricting strains had comparable levels of the four nuclease activities and had similar patterns of preference for the three substrates. In addition, mutants of E. coli B and K-12 that lack endonuclease I were as effective as their respective wild types in restricting T(*) phage.

Coliphages↗